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.
