Dopamine Revisited

Episode Transcript

(00:00):
Honestly,
I
didn't
quite
see
the
entire
end
of
it.
But
things
are
happening. 16 00:00:05,610 --> 00:00:00,-01 Eric:
You
need
to
see
the
end.
I
cut. 25 00:00:08,520 --> 00:00:00,-01 Dr. Josh Stout:
I
went
back
and
I
saw
some
things,
but.
Yeah. 36 00:00:10,650 --> 00:00:00,-01 Eric:
Hey.
So
today
is
Friday,
January
19th.
We've
taken
a
long
hiatus
due
to
holidays
and,
you
know,
illnesses
like
COVID,
which

(00:20):
are
happening
these
days. 63 00:00:21,780 --> 00:00:00,-01 Dr. Josh Stout:
We
had
holidays,
we
had
COVID. 70 00:00:23,310 --> 00:00:00,-01 Eric:
We
are
back
with
what
is
this
episode?
This
is
this
is
episode
two
of
season
two.
Hey,
Josh. 90 00:00:28,740 --> 00:00:00,-01 Dr. Josh Stout:
Hey,
Eric.
How's
it
going?
All
right.
Okay,
so
I've
been
preparing
for
a
class
that
I
am
going
to
be
teaching
Introduction
to
neurophysiology.
And
I've
been
focusing
on
dopamine.

(00:40):
And
it's
based
on
my
original
research
on
dopamine
that
I've
already
talked
about
a
little
bit.
But
as
I've
read
all
of
the
other
people
who
have
been
working
in
the
field,
I
thought
I
needed
to
address
some
of
what
they've
been
talking. 167 00:00:54,280 --> 00:00:00,-01 Eric:
I'm
sorry.
I
just
want
to
step
back.
What
is
the
name
of
the
course. 183 00:00:58,020 --> 00:00:00,-01 Dr. Josh Stout:
Introduction
to
neurophysiology? 187 00:01:00,540 --> 00:00:00,-01 Eric:
Is
this
of

(01:00):
course
you've
taught
before
now.
Oh,
fascinating. 198 00:01:03,450 --> 00:00:00,-01 Dr. Josh Stout:
This
is
not
a
course
I've
taught
before
and
I
am
not
teaching
the
way
the
course
is
normally
taught.
I'm
not
using
a
textbook.
I'm
making
it
all
up.
One
of
the. 232 00:01:11,310 --> 00:00:00,-01 Eric:
Yeah,
that's,
that's,
that's
one
of
the
things
I
like
about
this
that
you
wouldn't
use.
You
do
a
new
course.
You
have
to,
you
have
to
decide
what
you're
going
to
do
and
learn
it. 269 00:01:20,160 --> 00:00:00,-01 Dr. Josh Stout:
Exactly.
Yeah.
So

(01:21):
normally
when
someone
would
do
a
new
course
they
would
pick
the
textbook
and
then
the
syllabus
would
follow
the
textbook.
But
instead
I
have
a
bunch
of
ideas
and
then
I
have
to
find
papers
that
follow
those
ideas
and
I
have
to
do
this
for
undergraduates,
which
is
a
little
bit
complicated
because
some
of
the
papers
are
for,
say,
postdoctoral
students.
Yeah,
and
other
them.
Others
are
more
for
an

(01:41):
introduction
to
high
school
students.
And
in
between
there
is
some
things
my
students
can
actually
read
and
learn
from,
and
it's
difficult
to
find
exactly
what
they
are. 375 00:01:50,220 --> 00:00:00,-01 Eric:
This
is
great.
It's
making
you
do
a
lot
of
work. 387 00:01:52,110 --> 00:00:00,-01 Dr. Josh Stout:
It's
making
you
do
a
lot
of
work.
And
then
the
other
problem
is
I
disagree
with
the
fundamental,
fundamental
model
of
dopamine
as
it
is
presented.
And

(02:01):
so
the
readings
I
have
are
all
about
what
that
fundamental
model
is,
but
the
actual
lectures
are
going
to
be
something
else
entirely.
So
this
is
going
to
be
unusual
for
the
students
reading
something
that
then
the
professor
is
arguing
against.
So
if
they
study
and
learn
what
they're
reading
for. 469 00:02:18,420 --> 00:00:00,-01 Eric:
Undergraduates. 471 00:02:19,470 --> 00:00:00,-01 Dr. Josh Stout:
Yes,
it's
a
little
difficult.

(02:21):
So
what
I'm
doing. 481 00:02:22,620 --> 00:00:00,-01 Eric:
As
an
undergraduate,
I
have
a
lot
of
respect
for
undergraduates
and
the
work
that
they
do,
but
this
is
very
different.
Do
you
think
they
can
handle
it? 511 00:02:30,240 --> 00:00:00,-01 Dr. Josh Stout:
I
hope
so.
I
hope
so.
Mostly
it's
going
to
be
listening
to
me
and
I
explain
it
to
them.
And
then
the
background
reading,
which
they
wouldn't
do
anyway,
is
going
to
be
okay.
Sorry.
Honestly.

(02:42):
All
right.
So
they
were
going
to
be
listening
to
me
anyway
and
reading
my
notes.
That's
all
they
ever
do.
And
this
is. 573 00:02:47,760 --> 00:00:00,-01 Eric:
Interesting.
So
maybe
after
they
come
in
once
or
twice
and
they
hear
you
arguing
against
something
that
they
have
not
read,
they
might
get
interested
enough
to. 602 00:02:55,650 --> 00:00:00,-01 Dr. Josh Stout:
Actually,
they
might.
But
I
will
also
be
explaining
that
as
well.
So
they
just
want
everything
given
to
them

(03:02):
honestly.
And
I
will
be
doing
that.
And
I'm
happy
to
do
that.
And
if
they
need
to
do
any
extra
studying,
I
will
have
provided
papers
for
them
in
the
field. 655 00:03:12,360 --> 00:00:00,-01 Eric:
An
will
you
give
them
opportunities
to
show
that
they've
done
that
work? 669 00:03:15,990 --> 00:00:00,-01 Dr. Josh Stout:
I,
I
will
be
testing
them
and
they
will
have
to
know
some
things

(03:22):
and
then
they
will
be
making
a
poster
and
presenting
it.
So
anyway,
what
my
research
had
shown
is
that
dopamine
is
not
a
stimulant,
it's
inhibitory.
And
that's
what
started
everything.
And
I
tried
it
a
bunch
of
different
ways
and
it
was
quite
conclusive.
However,
there's
no
one
in
the
field
arguing
it
is
or
isn't
a
stimulus.
They're
just

(03:42):
accepted.
That
is
a
stimulus.
And
let's
move
on.
And
now
we'll
talk
about
what
dopamine
does.
So
they've
left
behind
the
whole
part
that
I'm
actually
disagreeing
with.
And
so
there's
a
new
understanding
of
how
dopamine
works.
Dopamine
had
been
understood
as
a
reward
substance.
It
is
now
no
longer
understood
is
the
thing
that
makes
you
feel
good.
It

(04:02):
is
understood
as
the
thing
that
makes
you
want
to
feel
good,
not
the
thing
that
makes
you
feel. 827 00:04:06,630 --> 00:00:00,-01 Eric:
And
this
is
as
of
when
When
did
this
change? 838 00:04:09,450 --> 00:00:00,-01 Dr. Josh Stout:
It
probably
started
in
the
nineties,
but
it
has
become
more
and
more
accepted
through
the
2000s.
And
so
this
is
mostly
coming
out
of
a
group
of
people
called
affective
psychology.
So

(04:22):
affect
so
in
a
was
an
A
Exactly.
So
these
are
people
who
are
behavioral
psychologists
who
are
studying
facial
expressions
in
response
to
things
and
in
this
case
what
they're
just
looking
at
is
do
you
stick
your
tongue
out
and
dislike
something
or
do
you
suck
heartily
on
the
thing
and
enjoy
it?
And
so
it
could

(04:42):
be
cocaine
or
it
could
be
sugar.
Those
are
pretty
much
the
two
things
they
use.
Mostly
sugar.
And
what
they've
shown
is
that
rats
or
people
like
sugar,
even
if
they
have
had
all
their
dopamine
blocked.
So
a
rat
who
has
had
their
brain
surgically
altered
too,
so
that
they're
not
producing
dopamine
will
happily
suck
on
sugar
water

(05:03):
and
or
cocaine.
And
someone
with
Parkinson's
disease
who
is
not
producing
dopamine
will
still
enjoy
the
taste
of
sugar
will
say,
Yes,
I
like
that
if
is
sweet. 1021 00:05:13,410 --> 00:00:00,-01 Eric:
So
so
the
idea
here
is
that
the
with
with
dopamine
with
no
dopamine
at
all,
you
can
still. 1041 00:05:19,710 --> 00:00:00,-01 Dr. Josh Stout:
Enjoy. 1043 00:05:20,310 --> 00:00:00,-01 Eric:
Joy
things. 1046 00:05:20,970 --> 00:00:00,-01 Dr. Josh Stout:
Yes.
Yes,
exactly.
And

(05:23):
people
who
have
low
dopamine
and
are
depressed
and
can
barely
go
to
bed
still
feel
pleasure.
So
there's
a
difference
between
the
idea
of
pleasure
and
wanting
something.
And
so
the
model
now
is,
is
that
dopamine
is
the
stimulant
that
causes
you
to
move
towards
a
reward.
And
it's
the
thing
that
makes
you
want
the
reward,

(05:43):
and
it's
the
measurement
of
the
reward.
So
this
is
the
current
understanding. 1123 00:05:47,390 --> 00:00:00,-01 Eric:
It's
both
the
the
the
pre
meaning,
the
thing
that
stimulates
you
to
move
towards
the
reward.
But
yet
it
is
also
the
measure
of
the
reward
received. 1152 00:06:01,620 --> 00:00:00,-01 Dr. Josh Stout:
But
not
the
reward.
Yes.
And
so
I
find

(06:03):
this
confusing. 1164 00:06:04,590 --> 00:00:00,-01 Eric:
But
how
can
it
how
can
it
be
something
before
you
receive
the
reward
and
then
also
after
you
get.
It's
both.
It's
both. 1189 00:06:12,120 --> 00:00:00,-01 Dr. Josh Stout:
And
it
kind
of
has
to
be
both.
Okay.
What
I
have
problems
with
the
idea
of
something
being
a
measure
of
a
reward,
but
not
the
reward
itself.
And
so
the
studies
show
that

(06:23):
if
you
block
dopamine,
an
R
in
a
rat,
it
falls
flat
on
its
face.
It's
not
going
to
move
anywhere.
It
has
no
desire
to
go
anywhere
ever
again
because
it
wants
nothing.
But
if
you
actually
saw
it. 1265 00:06:36,240 --> 00:00:00,-01 Eric:
So
the
idea
being
that
it
would
literally
lie
there
until
it
died. 1279 00:06:39,300 --> 00:00:00,-01 Dr. Josh Stout:
Yes,
but
if
you
put
sugar
water
in
its
mouth
because
it
doesn't
want
anything,

(06:43):
it
has
no
build
up
of
wanting
because
it
has
no
access
to
dopamine.
But
with
sugar
water
in
itself,
it
sucks
happily
on
the
sugar
water
so
it
doesn't
know
it
wants
the
sugar
water,
but
it
enjoys
getting
the
sugar
water.
So
this
is
a
separation
between
liking
and
wanting.
And
I
think
this
is
an
overly
complex
model
and
I
think
it
misses
the
fundamental
nature
of
what
dopamine

(07:04):
is,
which
is
an
inhibitory
reward
substance,
not
a
stimulatory
substance
that
makes
you
want
something,
something
that
it
would
be
inhibitory,
wouldn't
encourage
wanting
in
the
same
way,
whereas
something
that's
eye
stimulatory
also
would
then
be
a
problem

(07:24):
when
you've
finally
got
the
reward
because
it
would
make
you
move
away
from
the
reward
because
it's
stimulatory
rather
than
staying
there.
And
so
my,
my
model
of
dopamine
is
essentially
based
on
the
carrot
hanging
in
front
of
the
donkey.
And
I've
said
this
before,
but
now
I
understand
exactly
what's
going
on
a
little
bit
more.
So
the
ancient
Greeks,

(07:44):
when
they
thought
that
vision
worked
by
having
little
objects
go
into
your
brain
or
into
your
eyes
and
they
would
actually
be
sitting
in
your
eye.
And
so
now
we
understand
that
obviously
there's
nothing
going
into
our
eyes
from
the
outside. 1513 00:07:57,631 --> 00:00:00,-01 Eric:
I
actually
believe
that
there
was
a
physical
thing
going
into.
Right. 1526 00:07:59,881 --> 00:00:00,-01 Dr. Josh Stout:
So
in
some. 1530 00:08:00,361 --> 00:00:00,-01 Eric:
Way
we
know
that
there
is,
but
not
the
way
they
thought. 1543 00:08:02,941 --> 00:00:00,-01 Dr. Josh Stout:
Not
the
way
they
thought,
or
that
maybe
something
was

(08:04):
leaving
your
eyes
and
then
sending
it
out
and
that
information
was
coming
back
to
it.
They
had
all
sorts
of
ideas,
but
they
didn't
understand
how
anything
worked.
And
this
obviously
not
how
vision
works.
However,
if
you
think
of
an
organism
living
in
the
water
trying
to
find
something,
it's
going
to
be
using
smell
and
smell
and
taste.
If
you're
sitting
in
the
water,
essentiall
the
same
things.

(08:25):
And
so
smell
and
taste
are
little
bits
of
the
thing
you
want.
So
it's
a
little
bit
like
the
original
Greek
understanding
of
vision
to
start
to
see
something,
perceive
it
with
your
taste,
smell
in
the
water,
you're
actually
going
to
get
a
little
piece
of
that
thing
you're
tasting
smelling
in
order
to
know
you're
looking
for
the
right
thing.
Okay,
so
my
whole
model
is

(08:45):
based
on
that.
And
so
let's
say
there's
some
food
in
the
water
and
there's
little
bits
of
amino
acids.
The
number
one
amino
acid
that
we
all
respond
to
is
glutamate.
So
monosodium
glutamate
is
the
thing
that
makes
you
taste
things
as
savory
as
as
as
as
meat.
There's
only
five
flavors.

(09:05):
Two
of
them
are
rewards,
sweet
and
savory.
Two
of
them
make
babies
and
rats
stick
their
tongue
out
and
frown
so
sour
and
bitter.
And
then
salt
sort
of
depends
on
how
much
salt
you
have.
Both
the
glutamate
and
the
glucose
can
go
through
the
brain
blood
barrier
and
can
directly
stimulate
reward

(09:26):
pathways.
We
don't
know
exactly
how
all
of
this
works.
More
and
more
I'm
finding
out
if
it
if
I
don't
know
something
at
this
point,
it's
because
it
probably
hasn't
been
known.
I'm
not
boasting
that
I
know
everything
in
the
field.
I
just
keep
running
into
these
walls
that
just
find
out
that
we
really
don't
know
these
things
because
it
hasn't
been
tested. 1869 00:09:45,361 --> 00:00:00,-01 Eric:
So
the
bottles
have
a
black
box. 1877 00:09:46,921 --> 00:00:00,-01 Dr. Josh Stout:

(09:46):
That
they're
fake.
So,
so,
so
something
you
like
goes
in
sugar
or
glutamate
and
your
brain
says,
Suck
that
down,
eat
it
up
essentially. 1903 00:09:58,921 --> 00:00:00,-01 Eric:
Yeah. 1905 00:09:59,341 --> 00:00:00,-01 Dr. Josh Stout:
More
the
more
Exactly.
And
so
the
models
of
how
what
they
call
repetitive
behavior

(10:06):
appetite
stimulating
behavior
works
is
that
you
have
a
lack
of
something.
You
feel
uncomfortable,
hungry
or,
you
know,
sexually
aroused.
You
really,
really
want
to
go
find
a
reward.
A
lot.
By
the
way,
a
lot
of
this
modeling
was
done
by
men.
So
sex
is
a
lot
of
sort
of
the
metaphors
that
people
are

(10:26):
using.
Sex
definitely
has
a
desire
and
then
a
very,
very
obvious
reward
moment.
And
then
your
your
your
you're
no
longer
desiring
for
a
while
and
then
you
slowly
become
more
uncomfortable
as
you're
seeking
it
again.
However,
I
think
food
is
a
better
model
for

(10:47):
this
one
because
there
are
things
that
don't
have
sex
that
and
you
still
need
to
eat.
Food
comes
prior
to
sex
in
evolution.
And
unlike,
you
know,
sexual
release
when
you're
eating,
you
still
need
to
have
some
of
that
desire.
The
desire
and
the
eating
are
happening
at
the

(11:07):
same
time.
Mm
hmm.
So
it's
it's
a
it's
a
more
complicated
system.
And
I
think
it's
it's
more
fundamental. 2096 00:11:15,181 --> 00:00:00,-01 Eric:
And
more
inherently
complicated. 2101 00:11:17,671 --> 00:00:00,-01 Dr. Josh Stout:
System.
Yeah.
Yeah.
So
the
idea
is
you
haven't
eaten,
you
want
food,
you
then
seek
out
food.
You
see,
you
get
food
signals,
you

(11:27):
get
excited
because
you
get
those
food
signals.
You
seek
out
that
food,
you
get
the
food,
you're
getting
rewarded.
So
you
hold
still
and
eat
that
food.
And
at
this
point
you're
sated
and
you
don't
look
for
food
anymore
for
a
little
while.
And
then
the
whole
system
repeats
itself.
Okay?
So
in
my
system
that
glutamate
would
go
through
the
water,

(11:47):
glutamate
directly
stimulates
a
little
bit
of
dopamine.
And
so
the
dopamine
this
this
is
known. 2207 00:11:53,671 --> 00:00:00,-01 Eric:
It
enters
through
into
the
bloodstream,
right
into
the
brain. 2218 00:11:57,121 --> 00:00:00,-01 Dr. Josh Stout:
And
yes,
and
this
would
be
not
just
for
a
crayfish
and
shrimp,
which
I
was
studying,
but
also
for
a
human.
You
actually
get
glutamate
going
into
your
brain
when
when
you
eat
it. 2254 00:12:05,971 --> 00:00:00,-01 Eric:
Right
from
my
mouth

(12:07):
to
your
brain. 2262 00:12:07,741 --> 00:00:00,-01 Dr. Josh Stout:
Right
to
the
brain.
Right
to
the
brain.
Exactly.
So
these
these
are
conserved
pathways.
So
in
evolution,
we
talk
about
saying
that
you
see
everywhere
there's
a
well
conserved
pathway,
that
glutamate
stimulates
dopamine.
What
does
that
dopamine
do?
It
says,
let's
keep
looking
for
more
of
what
we're
getting.
We
want
to
find
more
of
this
food
so
a
crayfish

(12:27):
in
the
water
will
move
towards
a
gradient
that
gives
it
more
glutamate
in
one
direction. 2341 00:12:34,571 --> 00:00:00,-01 Eric:
Sends
a
little
glutamate
over
here,
I
sense
less.
No,
no.
Go
toward
food.
Good
things
more.
Yes,
yes,
yes.
Tuning
in.
A
radio.
So 2367 00:00:00,-01 --> 00:00:00,-01 .

Dr. Josh Stout: So 2369 00:00:00,-01 --> 00:00:00,-01 . (12:41):
undefined
So.
Every
time
they're
going
in
the
right
direction,
they
get
a
little
bit
more
reward.
The
dopamine.
Yeah.
So
this
is
my
model
now.
Yeah.
Okay.
So
imagine
you
have
a
donkey
running
after
that
carrot
on
a
stick.
Mm
hmm.
Okay,
so
the
donkey
can
see
the
carrot,
but
in
this
case,
there's
no
vision.
So
this
is
basically
a
donkey
looking

(13:01):
for
a
carrot
on
a
stick,
getting
little
bits
of
carrot
and
tiny
little
bits
of. 2450 00:13:05,011 --> 00:00:00,-01 Eric:
Carrot
a
little. 2454 00:13:05,461 --> 00:00:00,-01 Dr. Josh Stout:
Bit.
And
as
long
as
it
keeps
getting
tiny
little
bits
of
carrot,
its
nose
is
going
in
the
right
direction.
It
gets
no
carrot,
it
stops,
it
goes
in
the
opposite
direction.
So
my
understanding
of
what
researchers
have
been
doing
to
the
rats
when
they
give
when
they
block
dopamine
is
they've
been
blocking
those
little

(13:21):
bits
of
carrot.
And
so
that
that
little,
you
know,
donkey
mouse
crayfish
doesn't
get
those
little
bits
of
carrot.
And
so
no
longer
goes
for
the
carrot.
No
hope.
There's
no
hope.
There's
no
point
to
it.
What
dopamine
does,
in
my
opinion,
and
somewhat

(13:41):
the
research
supports
this,
is
it
signals
that
there
is
hope,
there
is
something
to
go
for.
Yeah,
yeah.
And
then
the
dopamine
goes
directly
to
both
reward
centers
and
places
in
your
brain
where
it
is
converted
into
epinephrine,
adrenaline,

(14:01):
or
epinephrine,
all
basically
the
same
thing.
So
the
dopamine
directly
becomes
a
stimulant. 2614 00:14:08,281 --> 00:00:00,-01 Eric:
Which
is
in
itself
a
reward,
is
it
not?
It's
related
to
a
reward
energy. 2630 00:14:14,521 --> 00:00:00,-01 Dr. Josh Stout:
I
suspect
these
are
related
to
the
dopamine
rewards
and
that
the
energy
is
there
to
keep

(14:21):
you
moving
so
that
you
get
a
little
bit
of
dopamine
you
and
say,
I'm
done.
I
say,
I
want
a
bigger
reward.
I'm
being
I'm
being
given
dopamine.
So
I'm
in
a
constant
real
time
measurement
of
I'm
going
in
the
right
direction,
I'm
aiming
for
the
right
thing,
and
I'm
getting
stimulated
a
little
bit
by
that
epinephrine
so

(14:42):
that
I
keep
moving. 2713 00:14:43,351 --> 00:00:00,-01 Eric:
So
then
what
happens
once
you
get
that
meal
and
you
get
the
big
payoff? 2729 00:14:46,891 --> 00:00:00,-01 Dr. Josh Stout:
Okay,
once
you
get
the
meal,
now
you're
getting
a
major
reward.
So
you're
getting
more
dopamine.
Yeah. 2748 00:14:52,081 --> 00:00:00,-01 Eric:
Like
all
at
once. 2753 00:14:52,981 --> 00:00:00,-01 Dr. Josh Stout:
All
at
once.
And
I
think
there
are
other
things
that
are
happening
as
well.
So
part
of
the
reason
that
people
think
that
dopamine
is

(15:02):
no
longer
a
reward,
but
it
is
just
a
thing
about
wanting
is
there
ordering
is
measuring
wanting.
Exactly.
It's
just
confusing
to
me.
Yeah,
exactly
How
much
money
do
I
have?
It's
the
money
in
my
head.
This
is
like
something
like,
not
the
money.
It's
some
sort
of
measurement
of
money,
but
not
money.
Anyway,
it
makes
sense
for
me.
It's
the
money
is
the
measure
of
the
money.
Yeah.
Anyway,
so
there
are
opiates
and
there

(15:22):
are
cannabinoids.
These
are
the
two
molecules
that
directly
signal
liking
as
the
afferent,
as
the
psychologists
call
it
an
afferent.
But
the
affective
psychologists.
So
they
they
there's
wanting
and
there's
liking.
And
so
dopamine
makes
wanting
in
their
opinion,
and
the
opiates
and
the
cannabinoids

(15:42):
make
liking.
Mm
hmm.
Okay.
So
I
think
both
sugar
and
glutamate
and
various
drugs
are
signaling
the
liking
things
in
these
two
very
small
pleasure
areas.
Dopamine
tends
to
it
signals
in
a
much
larger

(16:03):
area
called
the
nucleus
accumbens.
It's
underneath
the
brain,
essentially.
These
other
two
smaller
ones
are
in
it
and
they
talk
to
each
other.
So
the
two
smaller
pleasure
centers
make
dopamine
and
the
and
the
dopamine
signals
these
pleasure
centers.
So
what
you
do,
if

(16:23):
you
block
dopamine,
you
can
still
feel
the
opiates
and
the
cannabinoids.
So
I'm
not
denying
that
I
agree
with
that.
So
you
can
actually
block
dopamine
and
still
have
liking
dopamine
because
it's
also
a
reward,
in
my
opinion,
is
the
measure
of
the
reward,
because
it's
how
much
dopamine
you
make

(16:43):
when
you're
stimulating
the
opiates
and
the
cannabinoids.
They're
also
releasing
dopamine.
So
they're
also
saying,
yes,
you
got
that
reward.
So
that
reward
is
the
measure. 3068 00:16:53,311 --> 00:00:00,-01 Eric:
Of
the
reward.
So
the
opiates
and
the
cannabinoids
actually
not
only
turn
into
epinephrine,
but
they
also
talk
to
you.
The
dopamine
treat. 3093 00:17:03,481 --> 00:00:00,-01 Dr. Josh Stout:
Dopamine

(17:03):
turns
into
epinephrine
and
they
signal
more
dopamine
to
be
created. 3106 00:17:10,171 --> 00:00:00,-01 Eric:
So,
so
right,
so,
so
right.
So
dopamine
is
coming
and
going. 3119 00:17:15,871 --> 00:00:00,-01 Dr. Josh Stout:
It's
dopamine
is
coming
and
going.
And
all
of
these
things
talk
to
each
other.
It's
why
I
don't
deal
with
people
much,
because
all
of
these
centers
are
signaling
each
other
as
well.

(17:24):
And
a
lot
of
them
are
black
boxes.
This
is
all
done
with
functional
magnetic
resonance
imagery.
And
so
it's
correlation,
not
causation.
We
just
know
there
is
there
are
correlations
with
certain
things
that
we
call
liking
that
happen
in
these
pleasure
centers
that
happen
if
you
directly
inject
opioids
into
these
pleasure
centers,
you
get
the
like.
But
it's
like. 3216 00:17:43,601 --> 00:00:00,-01 Eric:
Inhaling
because
you

(17:44):
have
the
you
have
the
to
that
you
meant
the
cannabinoids
in
the. 3233 00:17:48,751 --> 00:00:00,-01 Dr. Josh Stout:
Opiate. 3235 00:17:49,121 --> 00:00:00,-01 Eric:
Opiates
are
specific.
But
the
way
you
describe
it,
the
the
the
dopamine
is
a
more
generalized
thing
that
affects
more.
So
if
you
were
to
shut
that
down,
the
sense
of
like
being
certain
that
there
can

(18:04):
be
no
satisfaction,
yes,
I
can.
And
then
and
then
once,
once
something
stimulates
the
cannabinoids
in
the
right
opiates,
then
ha.
But
then
once
it
stops,
there's
just
still
nothing
yet. 3306 00:18:16,291 --> 00:00:00,-01 Dr. Josh Stout:
Exactly.
Exactly. 3309 00:18:17,461 --> 00:00:00,-01 Eric:
And
you're
certain,
right? 3314 00:18:18,541 --> 00:00:00,-01 Dr. Josh Stout:
And
you're
certain.
Exactly.
Because
all
the
little
carrots
have
been
blocked,
Right?
All
those
little
carrots
that
that
shrimp
gets
have

(18:24):
been
blocked. 3339 00:18:25,081 --> 00:00:00,-01 Eric:
Well,
having
done
none
of
the
reading,
the
way
you
describe
it,
it
sounds
sounds
perfectly
reasonable. 3357 00:18:29,281 --> 00:00:00,-01 Dr. Josh Stout:
Exactly.
Yes.
So
small
amounts
of
dopamine
are
known
as
what's
called
tonic
dopamine
as
in
muscle
tone.
So
if
you
remove
tonic
dopamine,
you
have
no
muscle
tone,
you
just
collapse.
You
just
have
nothing.
And
so
this
constant
supply

(18:45):
of
small
rewards
in
the
form
of
tonic
dopamine
are
also
stimulating
epinephrine,
keeping
you
moving
towards
that
reward.
And
then
the
opioids
and
the
and
the
cannabinoids
are
the
sort
of
really
obvious
liking
signal.
But
dopamine
itself
is
a
liking
signal.
The
liking
signal
gets
stronger
in
the
presence

(19:05):
of
dopamine,
but
without
dopamine,
you
can
still
like
it.
So
again,
dopamine
is
liking
and
is
wanting
because
you
want
a
reward.
Now
think
about
what
these
things
are.
I'm
including
dopamine
with
opiates
and
cannabinoids.
All
three
of
these
things,
in
my
opinion,
are
not
stimulants.
They
are
inhibitory,

(19:25):
they're
not
inhibitory,
and
then
they
stop
something.
But
when
you
get
them,
you
stop
moving,
right?
You
stop
seeking
the
thing
you're
looking
for
because
you've
been
rewarded. 3530 00:19:34,291 --> 00:00:00,-01 Eric:
Except
the
dopamine,
which
you
said
very. 3538 00:19:35,881 --> 00:00:00,-01 Dr. Josh Stout:
Small
amounts
of
dopamine
keep
you
moving,
but
a
large
reward.
You
sit
and
eat
the
food
pellets,
right?
So
the
crayfish
stops
looking
around,
even
though
there's
a
lot
of
doping

(19:45):
in
the
water
near
it.
Right.
You
can
smell
dopamine,
but
it's
getting
the
dopamine.
It's
also
getting
the
opiates.
It's
also
getting
the
cannabinoid
because
it's
found
the
right
thing.
These
things
respond
to
a
whole
bunch
of
different
chemicals,
particularly
the
cannabinoids,
respond
to
a
bunch
of
fatty
acids.
And
so
the
crayfish
has
found
its
food
and
stopped
moving.
But

(20:06):
when
it's
looking
for
food,
it's
not
getting
little
bits
of
cannabinoids
and
it's
not
getting
little
bits
of
opiates
to
tell
it
where
to
go.
It's
getting
little
bits
of
dopamine.
So
dopamine
is
the
direct
measure
of
small
amounts
of
things
that
you
want
to
cause
you
to
seek
that
thing.
So
bright
lights,
flashing
colors,
good
smells
nice
sights,
things

(20:26):
you're
attracted
to,
that's
all
measured
by
dopamine,
but
it's
also
rewarded
by
dopamine
in
conjunction
with
these
other
reward
molecules.
In
the
current
model,
dopamine
would
be
a
stimulant.
They
would
be
inhibitory
because
they're
because
dopamine
is
not
a
reward,
in
my
opinion.
Dopamine
is
a
reward
and
is
just
like
these

(20:46):
other
ones.
They
in
large
amounts.
When
you
get
the
reward,
you
stop
moving.
It
would
be
really
interesting
to
see
if
you
can
cause
liking
in
the
absence
of
opioids
and
cannabinoids.
This
is
not
been
done
with. 3790 00:21:02,221 --> 00:00:00,-01 Eric:
Only. 3792 00:21:03,301 --> 00:00:00,-01 Dr. Josh Stout:
With
only
dopamine,
right?
So
because
you
can
block
dopamine,
you
can
still
see
that
there's
liking

(21:07):
in
the
presence
of
these
other
things.
It
hasn't
been
done
in
the
other
direction.
What
I
have
found
in
my
research
that
has
not
been
done
elsewhere
that
I'm
realizing
is
important
now
that
I've
been
going
over
this
stuff
is
I
have
shown
wanting
when
dopamine
is
blocked.
Now
I've
shown
this
in
a
short
term
so
I
can
give
something
glutamate

(21:28):
and
it
acts
just
like
there's
the
smell
of
food
in
the
water.
So
it's
exactly
the
same
without
dopamine,
just
just
glutamate.
It
acts
like
it
acts
like
there's
food
in
the
water.
So
naturally,
it
would
be
now
producing
its
own
glutamate
inside.
Yes,
I
can
give
it
Haloperidol,
which
blocks
dopamine,
and
it
still
runs
around
just
as
much
as
if
it
had
been
smelling
the
food. 3944 00:21:48,901 --> 00:00:00,-01 Eric:

(21:48):
Really. 3946 00:21:49,951 --> 00:00:00,-01 Dr. Josh Stout:
I
don't
know
if
this
would
continue
in
a
longer
term
project.
So
one
thing
that
I've
seen
in
a
couple
of
a
couple
of
bits
of
research
that
tends
to
be
downplayed
is
after
you
give
something
Haloperidol,
there
seems
to
be
an
initial
excitatory
phase.
So
when

(22:09):
something
gets
haloperidol,
at
first
it's
getting
no
carrot,
so
it
really
wants
carrots.
And
so
at
first
it'll
push
that
button
a
little
bit
faster
and
then
it
will
give
up.
And
so
I
might
have
been
only
doing
my
experiments
on
crayfish
in
that
initial
bit.
And
so
initially
Haloperidol
has
no
particular
effect
because
there
wasn't
that
much
dopamine

(22:29):
anyway,
right?
There
was
only
little
tiny
carrots.
And
that
in
that,
in
that
crayfish
donkey
brain.
And
so
by
blocking
it,
it
still
wants
stuff.
It's
still,
it's
still
seeking
how
it
knows
what
to
want.
I
don't
know.
I'm
wondering
if
there
aren't
more
than
one
reward.
We
know
there's
these
two
other
molecules.
It
might
be
getting
small

(22:49):
amounts
of
cannabinoids.
It
might
be
getting
small
amounts
of
of
of
opioids.
So
there
might
be
more
than
one
reward
and
desire
pathway.
We
know
that
people
who
are
blocked
from
getting
say,
you
know,
heroin
really,
really
want
more
heroin.
Mm
hmm.
And
that

(23:09):
is
a
measurement
of
reward
based
on
opiates.
Now,
opiates
are,
again,
related
to
dopamine.
So
the
current
model
is
all
of
that
wanting
for
heroin
is
coming
from
wanting
triggered
by
dopamine
that
is
then
satisfied
by
the
presence
of
opium.
Okay.

(23:30):
So,
so,
so
so
the
idea
is
that
the
wanting
has
nothing
to
do
with
the
opioids.
I
disagree.
I
think
all
the
rewards
that
reward
that. 4235 00:23:40,651 --> 00:00:00,-01 Eric:
Kind
of
intense
wanting
is
only
created
by
the
presence
of
the
opioids.
Well,
by. 4251 00:23:45,721 --> 00:00:00,-01 Dr. Josh Stout:
The
lack
by
by
what
you
used
to
have,
and
now
you
lack. 4265 00:23:48,631 --> 00:00:00,-01 Eric:
It.
But
but
it's

(23:50):
only
created
by
the
initial
elevated
level,
which
is
then
a
renormalization.
Right.
And
then
the
lack. 4287 00:23:58,501 --> 00:00:00,-01 Dr. Josh Stout:
Right,
right,
right.
So,
so
the
the
model
of
wanting
being
a
separate
function
from
liking
I
disagree
with
I
think
the
more

(24:10):
you
get
what
you
like,
yeah.
The
more
you
want
it.
And
so. 4324 00:24:14,371 --> 00:00:00,-01 Eric:
It
just
seems
like. 4329 00:24:15,631 --> 00:00:00,-01 Dr. Josh Stout:
Exactly
my. 4332 00:24:16,531 --> 00:00:00,-01 Eric:
Model
isn't
like
that. 4337 00:24:17,811 --> 00:00:00,-01 Dr. Josh Stout:
Exactly.
My
model
is
simpler. 4343 00:24:19,831 --> 00:00:00,-01 Eric:
Why
would
that
not
be
so
right? 4351 00:24:21,511 --> 00:00:00,-01 Dr. Josh Stout:
So
so.
So
some
of
the
arguments
against
this
is
if
someone
is
a
cocaine
addict
and
you
block
dopamine,
it
reduces

(24:30):
their
cravings
for
cocaine,
but
they're
still
happy
to
ingest
the
cocaine
when
they
get
it.
So
just
like
the
rat
given
Haloperidol.
Yeah.
However,
it
never
lasts.
It
never
works
because
there
is
this
more
or
less
constant
lack
of
cocaine,

(24:51):
which
even
if
you
are
not
feeling
the
wanting
associated
with
dopamine
for
some,
somehow
you
still
want
it.
So
I
think
the
dopamine
is
a
larger
signal
for
desire,
but
that
the
opioids
and
the
cannabinoids
are
also
rewards
and
also
signals
of
desire. 4461 00:25:10,531 --> 00:00:00,-01 Eric:
How
could
anything
be

(25:11):
only
one
thing
when
everything
in
life
tells
us
that
everywhere
we
look,
nothing
is
any
one
thing? 4484 00:25:19,411 --> 00:00:00,-01 Dr. Josh Stout:
Well,
it's
true.
And
it's
it's
it's
no
matter
what
model
you
use,
you
have
to
be
able
to
go
back
and
forth
between
wanting
and
the
gratification
of
the
thing
you
want. 4518 00:25:29,041 --> 00:00:00,-01 Eric:
And
also,
it's
fascinating.
I
mean,
the
first
time
you
told
me

(25:31):
the
dopamine
actually
directly
just
turns
into
epinephrine,
It's
like.
But
so
so
one
thing
is
literally
not
one
thing.
Right?
Right.
Literally
becomes
something
else
becomes
something
on
the
body. 4562 00:25:44,701 --> 00:00:00,-01 Dr. Josh Stout:
Long
Right.
So
the
dopamine
is
the
reward
and
epinephrine
is
the
stimulant
to
move
towards
the
reward.
And
so
if
you
have
a
little
bit
of
dopamine,
it's
turning
into

(25:51):
a
little
bit
of
epinephrine
and
you
move
towards
it.
Now,
no
matter
what
model
you
use,
once
you
start
defining
things
strongly
in
a
model,
there's
going
to
be
problems
with
your
model.
But
I
think
I'm
answering
more
of
the
problems
with
the
existing
model,
with
my
model
than
the
one
where
you're
separating.
Dopamine
is
not
a
liking

(26:12):
drug.
It's
a
wanting
drug
purely
on.
One
of
the
things
that
makes
more
sense
in
my
model
than
in
the
existing
one
is
ADHD.
So
the
current
model
of
ADHD
is
you're
hyperactive
because
you
have
a
low
amount
of
dopamine.
So
if
dopamine
is
is

(26:32):
a
stimulant,
then
more
dopamine
would
not
be
recommended.
Whereas
if
dopamine
is
inhibitory
and
you
give
someone
who
has
ADHD,
dopamine,
they're
going
to
be
able
to
concentrate
better.
And
this
is
what
we
actually
do,
right?
So
when
people
have
ADHD,
we
give
them
stimulants
that
stimulate
dopamine. 4752 00:26:52,681 --> 00:00:00,-01 Eric:

(26:52):
Yes. 4754 00:26:53,431 --> 00:00:00,-01 Dr. Josh Stout:
And
that
dopamine. 4758 00:26:54,511 --> 00:00:00,-01 Eric:
Oh,
I
never
does
this.
This
stimulants.
What
they
do
is
they
stimulate
dopamine. 4773 00:26:58,741 --> 00:00:00,-01 Dr. Josh Stout:
Yes,
exactly.
You
realize
the
amphetamines.
Exactly.
And
yes,
you
get
stimulated
because
that
some
of
that
dopamine
is
turning
into
epinephrine
and
it
stimulates. 4799 00:27:07,231 --> 00:00:00,-01 Eric:
Activity. 4801 00:27:07,801 --> 00:00:00,-01 Dr. Josh Stout:
And
it
will
be
activity.
And
this
holds
true
for
ADHD
people,
ADHD
people
as
well
as
anyone

(27:12):
else.
There's
some
people
out
there
who
think
that
somehow
stimulants
don't
affect
ADHD
people,
that
for
whatever
weird
reason
in
their
brain
that
stimulants
are
inhibitory
to
ADHD.
But
it's
not
true.
Stimulants
are
stimulating
because
of
epinephrine.
Your
heart
will
go
faster,
your
appetite
will
be
reduced.
All
of
these
things,
however,
the
dopamine

(27:32):
is
making
you
feel
like
you've
found
the
thing
you're
looking
for.
And
so
you
stop
some
of
that
seeking
behavior
that
is
associated
with
low
dopamine.
So
in
that
a
repetitive
cycle
that
we
are
talking
about,
people
who
have
ADHD
are
always
in
that
part
where
they're
a
little
uncomfortable
and
they're
starting
to
look
for
that

(27:53):
next
set
of
rewards. 4939 00:27:55,171 --> 00:00:00,-01 Eric:
Whatever
that
is. 4943 00:27:56,011 --> 00:00:00,-01 Dr. Josh Stout:
Whatever
that
is,
no
idea
what
is
right.
And
this
is
the
weird
thing
about
our
brains
is
we
don't
know
one
dopamine
from
another.
So,
you
know,
we
can
we
can
we
can
transfer
one
kind
of
reward
for
another.
So
when
we're
depressed,
we
eat
lots
of
food
because
it
makes
us
feel
better,
because
we
get
those
rewards
and
we're
less

(28:13):
depressed.
All
of
these
things.
Yeah,
Yeah.
So,
so
this
is
what
people
with
ADHD
are
always
looking
for.
And
also,
I
think
why
they
can
hyperfocus.
So
one
of
the
sort
of
superpowers
of
ADHD
is
yes,
you
have
lack
of
focus,
you're
always
looking
for
other
things.
When
you
really
get
into
things,

(28:33):
you
see
nothing
else
in
the
world. 5070 00:28:35,251 --> 00:00:00,-01 Eric:
The
whole
world
disappears. 5075 00:28:36,181 --> 00:00:00,-01 Dr. Josh Stout:
And
I
think
what's
happened
is
you've
triggered
that
dopamine
reward.
When
you
found
something
you
really
like,
you
get
into
it.
Even
deeper
than
other
people
have
because
you've
been
so,
so
seeking
that.
Now
you've
found
your
reward.
And
again,
it
can
be
anything.
It's
not
it.

(28:53):
You
could
become
a
drug
addict
or
you
could
become
a
painter,
or
it
could
be
anything
that
gives
you
that
satisfaction.
There
is
no
difference
to
the
dopamine.
It's
all
it's
all
the
dopamine.
But
fundamentally,
I
think
dopamine
is
an
inhibitory
reward.
It
is
not
stimulatory
and

(29:13):
that
it
is
something
where
you
need
small
amounts
to
move
towards
a
goal,
but
it
is
still
the
reward
given
to
you
with
the
goal.
It
works
with
other
rewarding
molecules,
the
cannabinoids
and
the
opiates.
But
it
itself
is
also
a
rewarding
molecule
and

(29:33):
acts
just
like
them.
When
you
get
a
big
reward,
you
sit
still
and
just
smile,
right?
That's
what
dopamine
does
and
it's
coming
out
of
nowhere
to
do.
And
that's
what
the
opiates
do.
And
when
you
don't
have
those
things,
you
start
seeking
them.
This
is
what
all
of
these
things
do.
And
so
I
think
rewards
are
the
measure
of
the
of
of
the
wanting. 5288 00:29:52,381 --> 00:00:00,-01 Eric:
Okay.
The
rewards
are
the
measure

(29:54):
of
the
wanting.
Yeah. 5299 00:29:56,071 --> 00:00:00,-01 Dr. Josh Stout:
So
the
bigger
the
reward,
the
more
you
will
want
it.
If
you
see
a
bigger
carried
out
there,
you're
going
to
want
it
more
fascinating.
All
right.
So
that
was
basically
my
talk
for
a
short
while. 5338 00:30:04,771 --> 00:00:00,-01 Eric:
So
what
you've
so
you
what
you've
done
though
before
I
before
I
let
you
finish,
you've
turned
it
around.
It's
it's
the
measure
of
the
wanting,
not
the
measure
of
the
reward. 5372 00:30:14,101 --> 00:00:00,-01 Dr. Josh Stout:
Right.
So
that

(30:14):
what
want
want
wanting. 5380 00:30:17,761 --> 00:00:00,-01 Eric:
The. 5382 00:30:19,351 --> 00:00:00,-01 Dr. Josh Stout:
Yeah.
I
mean
so,
so
previous
to
this
it
would
be
something
that
gave
you
a
lot
of
dopamine,
could
make
you
want
something
but
then
you
might
not
enjoy
it
when
you
got
it
in
this,
in
this
model,
when
you
really
enjoy

(30:34):
something,
it
makes
you. 5431 00:30:36,151 --> 00:00:00,-01 Eric:
Want
that
you
wanted
that
much
more. 5439 00:30:38,161 --> 00:00:00,-01 Dr. Josh Stout:
That
much
more.
Exactly.
And
to
me,
that
makes
much
more
sense. 5452 00:30:41,461 --> 00:00:00,-01 Eric:
Everything
you've
been
saying
just
seems
to
make
sense.
All
right.
Well,
yeah.
Thanks,
Josh.
That
was
fascinating. 5471 00:30:46,831 --> 00:00:00,-01 Dr. Josh Stout:
Yeah.
Just
a
quick
rundown
on
where
I'm
going
and
what
my
next
semester
is
going
to
be,
and
then
I'm
going
to
start
doing
some
experiments
and
I'll
I'll
have
some
more
answers.
But
this
is
going
to
take
you. 5513 00:30:54,241 --> 00:00:00,-01 Eric:
So,
so

(30:54):
so
I
mean,
this
that
that
was
my
next
question
is
how
do
you
how
do
you
find
results
that
prove
what
it
is
that
you're
saying? 5543 00:31:03,551 --> 00:00:00,-01 Dr. Josh Stout:
Well,
nothing
is
ever
proven.
But
I
can
I
can
I
can
show
things
in
that
that'll
support
my
my
ideas.
And
the
main
one
is,
is
that
dopamine
is
not
stimulatory.
I
love
and
I
can
show
it
again
and
again
and
again. 5588 00:31:15,091 --> 00:00:00,-01 Eric:

(31:15):
So
so
then
am
I
sitting
here
hearing
the
genesis
of
of
the
work
of
many
students
to
come?
Yes.
Oh,
I
love
it. 5613 00:31:23,761 --> 00:00:00,-01 Dr. Josh Stout:
Absolutely.
Yes.
This
is
going
to
be
years
of
work. 5624 00:31:25,981 --> 00:00:00,-01 Eric:
Fantastic.
All
right.
Have
fun,
everyone.
All
right.
Thank
you.
It's
Josh.