The proposed research is designed to investigate the neural mechanisms of operant conditioning.
The specific aim i s to attempt to define the functional unit in the brain for positive reinforcement. Does the individual brain cell have the capacity for operant conditioning, or must some larger organizational unit -- perhaps the substrate of the whole response itself -- be identified? And even if the operant conditioning of single units can be demonstrated does such a cellular process contribute significantly to behavioral operant conditioning? These questions will be evaluated primarily by use of two recently developed methods for the localization of chemical reinforcement effects in the brain. In the first method (brain self-administration), a behavioral response will be reinforced by direct injections of transmitters or drugs into specific brain regions. In the second method (""""""""neuronal operant conditioning""""""""), the activity of neurons in brain slices form the same regions will be reinforced by cellular application of the transmitters and drugs. Appropriate pharmacological antagonist will be used to identify the brain receptors that may be associated with reinforcing effects in the two tests. The experimental plan proposes concurrent use of both operant conditioning methods in an attempt to correlate the reinforcing effects of transmitter and drugs at the behavioral and cellular levels. It is widely believed that the pathophysiology of certain mental disorders -- such as schizophrenia, mania, and depression -- involves dysfunction of behavioral reinforcement mechanisms. Elucidation of the biology underlying these mechanisms may open new approaches to the treatment of mental disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA005107-03
Application #
2117435
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1990-04-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1994-03-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Pharmacology
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
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Self, D W; Terwilliger, R Z; Nestler, E J et al. (1994) Inactivation of Gi and G(o) proteins in nucleus accumbens reduces both cocaine and heroin reinforcement. J Neurosci 14:6239-47
Stein, L; Xue, B G; Belluzzi, J D (1993) A cellular analogue of operant conditioning. J Exp Anal Behav 60:41-53
Xue, B G; Belluzzi, J D; Stein, L (1993) In vitro reinforcement of hippocampal bursting by the cannabinoid receptor agonist (-)-CP-55,940. Brain Res 626:272-7
Self, D W; Stein, L (1993) Pertussis toxin attenuates intracranial morphine self-administration. Pharmacol Biochem Behav 46:689-95
Self, D W; Stein, L (1992) The D1 agonists SKF 82958 and SKF 77434 are self-administered by rats. Brain Res 582:349-52