Date: April 2nd, 2009

Seminar Title: "Dopamine and effort in food intake control"

Speaker's Name and Affiliation:

• John Salamone
• University of Connecticut

Presiding Chair: Harry R. Kissileff, Ph.D.

Rapporteur: Kathleen L. Keller, Ph.D.

Attendees and their Affiliation:

Kathleen Keller	Columbia/Obesity Research Center
Harry Kissileff	Obesity Research Center
Michael Lewis	Hunter
Merce Correa
Susan Carnell	RC/CU
Karen Ackroff	Brooklyn College
Khalid Touzani	Brooklyn College
Steven Zukerman	Brooklyn College
Joe Vasselli	ORC
Carol Maggio	ORC
Rhoda Gruen	Columbia
Ralph Norgren	Penn State
Gerry Smith	Weill Medical College
Timothy Walsh	Columbia
Sally Lederman	Columbia
Ryan Ward	Columbia
Kathleen Taylor	Columbia
Michael Devlin	Columbia
JA Grinker	University of Michigan

Summary: (Prepared by the speaker)

It has become evident that there are substantial problems with the hypothesis that nucleus accumbens dopamine (DA) directly mediates the rewarding or primary motivational characteristics of natural stimuli such as food. This area of research is undergoing a substantial restructuring, and current hypotheses of accumbens function tend to focus on the role of this structure in aspects of instrumental learning, reward prediction, incentive salience and behavioral activation. The present review discusses the neurochemical interactions involved in the effort-related functions of nucleus accumbens and associated forebrain areas. The effects of accumbens DA depletions on food-seeking behavior are highly dependent upon the work requirements of the task. Lever pressing schedules that have minimal work requirements are largely unaffected by accumbens DA depletions, while reinforcement schedules that have high work requirements are substantially impaired by accumbens DA depletions. In addition, interference with accumbens DA transmission exerts a powerful influence over effortrelated decision making. Rats with accumbens DA depletions reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead they select a less-effortful type of food-seeking behavior. Recent studies indicate that adenosine and DA interact in the regulation of effort-related processes. Intra-accumbens injections of drugs that stimulate adenosine A2A receptors can induce impairments that are similar to those produced by interference with DA transmission, while adenosine A2A antagonists can reverse the effects of DA antagonists. Studies of the neurochemical interactions regulating effort-based processes may have implications for understanding drug abuse, as well as energyrelated disorders such as psychomotor slowing, fatigue or anergia in depression.

Discussion:

Q. You are talking specifically about the dopamine reward system hypothesis. Berridge makes distinctions in that system.
A. I have a slide about that. I¡¯ll go through that later.

Q. How high is the barrier in the T-maze?
A. 44 cm

Q. How do you know this isn¡¯t a motor effect?
A. We don¡¯t, it could be a number of things.

Q. How do you interpret what you said earlier, that when they see the barrier, the mice will go to the other end?
A. They can climb the barrier, but they don¡¯t.

Q. Why?
A. They have a bias toward the low effort behavior.

Q. In those experiments with changing reward, did you use a different concentration of sugar?
A. We haven¡¯t, but we are planning to use alcohol in the future.

Q. Are these peripheral injections of haloperidol?
A. They are all IP injections.

Q. What does EPN stand for?
A. Entero periventricular nucleus.

Q. What about using a progressive ratio schedule of reinforcement?
A. We¡¯ve not done that yet, but we should.

Q. Have you looked at delta Fos-beta?
A. We did, but the basal conditions didn¡¯t work properly.

Q. How did you measure GABA?
A. Electron chemical detection.

Q. The slide with Berridge¡¯s theory on it seems to suggest that dopamine does not change wanting, but only the ability of the animal to make the effort to do something.
A. I think that¡¯s a good description.

Q. Does dopamine manipulation affect licking response or mouth motor muscles?
A. Smith and Fowler both looked at that. Dopaminergic manipulated affected lick force and lick duration.

Q. If you have a non-deprived animal, you should still see a preference for palatable food over chow. If you gave haloperidol, would they then go for chow?
A. I want to say no, but old literature did see an increase in food intake with low level haloperidol.

Q. Smith has shown that giving raclopride changes the reinforcing value of food. How do you explain those findings?
A. Smith gave a much higher dose of raclopride. In these different doses, you get low level changes in effort.

Q. Have you looked at self-stimulation?
A. Darryl Neale published studies showing that intra accumbens DA resulted in self-stimulation.