From: gts (gts@optexinc.com)
Date: Thu Aug 22 2002 - 22:26:55 MDT
Rafal wrote:
### Can you point me to the research showing that the release of
dopamine in NAc (a physical event) has the experiential correlate of
"pleasure"? I thought we are still far from being able to explain
conscious experiences in mechanistic terms...
Yes I can point you to such research.
Most current research in this area has come from researchers in the
field of addictionology. This is so because an addiction is essentially
a disease or malfunction of the neurological reward system.
The first scientist to explore this field in detail was the psychologist
James Old, who discovered in the 50's that rats given the ability to
electrically stimulate their own brain reward centers would do so
without stopping, until they died from exhaustion. They would endure
severe pain from electrical shocks to push the lever that stimulated
their reward centers.
Similar experiments were performed later, but these later experiments
the with rats were given the ability to inject cocaine into their NACs.
The results were the same.
By the way, I should modify my original statement a bit here, and state
more generally that the experience of pleasurable reward arises in the
mesolimbic system. This part of the brain includes the NAC. Rewarding
experiences generally arise from dopamine release in the NAC but some do
seem to be a result of dopamine release in other parts close-by in the
mesolimbic system.
I am a personal friend and colleague of Dr. Kenneth Blum, a
neuroscientist famous for identifying a category of symptoms he termed
"The Reward Deficiency Syndrome." This syndrome has a genetic basis.
Here is the abstract of a paper he published:
ABSTRACT
Reward deficiency syndrome: a biogenetic model for the diagnosis and
treatment of impulsive, addictive, and compulsive behaviors.
J Psychoactive Drugs 2000 Nov;32 Suppl:i-iv, 1-112 (ISSN: 0279-1072)
Blum K; Braverman ER; Holder JM; Lubar JF; Monastra VJ; Miller D; Lubar
JO; Chen TJ; Comings DE
Department of Biological Sciences, University of North Texas, Denton,
Texas, USA.
The dopaminergic system, and in particular the dopamine D2 receptor, has
been implicated in reward mechanisms. The net effect of neurotransmitter
interaction at the mesolimbic brain region induces "reward" when
dopamine (DA) is released from the neuron at the nucleus accumbens and
interacts with a dopamine D2 receptor. "The reward cascade" involves the
release of serotonin, which in turn at the hypothalmus stimulates
enkephalin, which in turn inhibits GABA at the substania nigra, which in
turn fine tunes the amount of DA released at the nucleus accumbens or
"reward site." It is well known that under normal conditions in the
reward site DA works to maintain our normal drives. In fact, DA has
become to be known as the "pleasure molecule" and/or the "antistress
molecule." When DA is released into the synapse, it stimulates a number
a DA receptors (D1-D5) which results in increased feelings of well-being
and stress reduction. A consensus of the literature suggests that when
there is a dysfunction in the brain reward cascade, which could be
caused by certain genetic variants (polygenic), especially in the DA
system causing a hypodopaminergic trait, the brain of that person
requires a DA fix to feel good. This trait leads to multiple
drug-seeking behavior. This is so because alcohol, cocaine, heroin,
marijuana, nicotine, and glucose all cause activation and neuronal
release of brain DA, which could heal the abnormal cravings. Certainly
after ten years of study we could say with confidence that carriers of
the DAD2 receptor A1 allele have compromised D2 receptors. Therefore
lack of D2 receptors causes individuals to have a high risk for multiple
addictive, impulsive and compulsive behavioral propensities, such as
severe alcoholism, cocaine, heroin, marijuana and nicotine use, glucose
bingeing, pathological gambling, sex addiction, ADHD, Tourette's
Syndrome, autism, chronic violence, posttraumatic stress disorder,
schizoid/avoidant cluster, conduct disorder and antisocial behavior. In
order to explain the breakdown of the reward cascade due to both
multiple genes and environmental stimuli (pleiotropism) and resultant
aberrant behaviors, Blum united this hypodopaminergic trait under the
rubric of a reward deficiency syndrome.
***
You might be thinking that normal healthy reward may not be mediated by
the same mechanisms that mediate the reward that comes from substance
abuse. However there is plenty of evidence to show a very strong
connection between the two types of reward. For example the healthy
behavior of exploring one's environment ("novelty seeking") causes a
release of dopamine in the NAC virtually identical to that caused by
cocaine.
ABSTRACT:
Regional and temporal differences in real-time dopamine efflux in the
nucleus accumbens during free-choice novelty.
Brain Res 1997 Nov 21;776(1-2):61-7 (ISSN: 0006-8993)
Rebec GV; Christensen JR; Guerra C; Bardo MT
Department of Psychology, Indiana University, Bloomington 47405, USA.
rebec@indiana.edu.
To assess dopamine efflux during novelty-seeking behavior in rats,
fast-scan cyclic voltammetry in the nucleus accumbens was combined with
free-choice entry into a novel environment. Cyclic voltammograms,
confirmed by in vitro testing, revealed that entry into novel, but not
familiar, surroundings increased dopamine efflux in a regionally and
temporally distinct pattern. Whereas dopamine failed to change in the
core region of the accumbens and overlying neostriatum, an abrupt
increase occurred in accumbal shell, a limbic-related area implicated in
goal-directed behavior. Although the dopamine response was confined to
the brief period of entry into novelty (approximately 8 s duration), a
less rapid and more persistent dopamine change (> 20 s duration)
occurred in the shell-core transition zone, the so-called shore. These
results suggest that novelty mimics other positively reinforcing stimuli
in enhancing dopamine transmission in the nucleus accumbens, but the
regional and temporal heterogeneity of this effect may represent
different aspects of accumbal dopamine function.
***
Drugs of abuse come in many forms (narcotics, amphetamines, alcohol,
nicotine, etc). On the surface they each appear to work through
different channels and neurotransmitters. However it is now known that
they *all* cause a release (or an inhibition of reuptake) of dopamine in
the NAC. This is their common function, and the end of the reward
cascade. Moreover it appears that all healthy rewarding experiences of
life do the precisely same thing, (though not usually with the same
strength or intensity, which is of course a primary reason that drugs of
abuse can destroy one's personal life).
Natural healthy reward stimuli can also become addictive for the same
reason that reward from drugs is addictive. For example risk-taking has
some adaptive value, which in modern society results in gambling
addiction. Sexual addiction and food addiction are also very common.
These are subversions of natural adaptive traits, linked to specific
polymorphisms of the genes that code for the dopamine receptor and the
dopamine transporter.
Here is an interesting paper titled "Anticipation of Increasing Monetary
Reward Selectively Recruits Nucleus Accumbens."
http://www-psych.stanford.edu/~knutson/bk01jn.pdf
Here is an interesting research abstract in with the authors state that
"The nucleus accumbens is the engine of the reward response."
http://www.heroin.org/dopamine/
For more references, I suggest you do a google search on such words as
"James Old"
"reward nucleus accumbens"
"reward deficiency syndrome"
It's a fascinating subject.
-gts
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