GROUP I MGLURS AND COCAINE SENSITIZATION

Medical University Of South Carolina, Charleston SC

Investigators

Abstract

DESCRIPTION Sensitization to psychostimulants upon repeated administration involves enduring biochemical changes that underlie an augmented behavioral output. These long-term changes manifest within the nucleus accumbens (NA), in part, as enhanced dopaminergic neurotransmission that is implicated in psychostimulant-induced paranoid psychosis and drug relapse in recovering addicts. The role that specific metabotropic glutamate receptor (mGluR) sub-groups play in this event is unclear. The proposed studies herein are intended to investigate group I mGluR involvement in the lasting behavioral and biochemical changes seen in cocaine sensitization. This will be accomplished by conducting the following studies at both 24 hours (early) and 3 weeks (late) withdrawal from drug administration: 1) Investigation of the role that group I mGluRs play in behavioral expression of cocaine sensitization; 2) Analysis of protein changes in mGluR1 and mGluR5 as well as group I-associated regulatory proteins Homer 1a and homer 1 b/c in brain regions pertinent to cocaine sensitization. These studies will examine potential biochemical correlates to the behavioral response demonstrated above; and 3) Assessment of the ability of group I mGluRs to elevate intracellular IP3 level in sensitized animals. These studies will offer insight into the functional regulation of intracellular mechanisms associated with Group I mGluRs in animals sensitization to cocaine. Taken together, results obtained from this proposal may divulge possible novel pharmacological interventions in the treatment of drug-induced neurological aberrations.