ACCUMBAL GLUTAMATE RECEPTORS IN COCAINE CONDITIONING

$110,273S06FY2001GMNIH

University Of Puerto Rico Rio Piedras, San Juan PR

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Abstract

Description (Adapted from Application): Drug abuse has become a major social and medical problem in the world. Presently, it is estimated that there are over 2 million regular drug users in the USA. Clinical studies have reported that one of the major problems confronted by substance abusers during periods of abstinence is their susceptibility to "cravings" for the drug that may arise in an environment associated with drug use. In addition, behavioral studies have shown that drug-related cues can acquire reinforcing properties through classical conditioning. However, little is known about the biological basis of cue-elicited drug craving. One of the main goals of neurobiological research is to study the different neural systems and molecular mechanisms involved in drug dependence. The nucleus accumbens, as part of the ventral striatum, have previously been implicated in mediating the motor activation and reinforcing effects of psychostimulant drugs such as cocaine. In addition, studies have demonstrated that the accumbens regulates different learning and memory functions and that excitatory amino acid (EAA) neurotransmission from cortical and limbic projections to these striatal regions modulate these functions. Furthermore, the metabotropic glutamate receptor (mGluRs) is a type of EAA receptor found in the striatum that seems to have modulatory effects in synaptic plasticity and learning. These studies are aimed to investigate the role of EAA inotropic and metabotropic receptors within the nucleus accumbens in the acquisition and expression of cocaine-induced environment-specific conditioning. The two major goals of the proposed experiments are: 1) to investigate the role of EAA receptors within the nucleus accumbens subregions in mediating cocaine conditioning. 2) to characterize the functional role of EAA metabotropic receptors (mGluRs) in the associative learning present in this conditioning. Results from the proposed research plan may provide new knowledge on the neuroanatomical substrates and receptor specificity involved in the control of cocaine-elicited conditioning.

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