The present project proposes to examine the putative enhancing effects of benzodiazepine (BDZ) pretreatment on intravenous opiate drug reward. Clinical case studies have reported numerous examples of apparent opiate drug enhancement in opiate abusers who self-medicate with an oral BDZ tranquilizer prior to their opiate injection. In our laboratory, we have been able to confirm this BDZ-opiate reward interaction in rats. Our preliminary results have demonstrated a reliable potentiation in the size of the heroin-induced place preferences in animals pretreated with low doses of the BDZ, alprazolam; an effect which is blocked by treatment with the BDZ receptor antagonist, flumazenil. The maximal effect is produced at low doses of both heroin and alprazolam that do not produce evidence of drug reward when administered alone. The current proposal builds upon these results in the form of two specific aims: 1) to replicate and extend the preliminary findings by testing the ability of buspirone (a non-BDZ anxiolytic agent) to facilitate opiate reward and to investigate the BDZ-opiate interaction with other measures of drug reward (i.e., operant self-administration); and 2) to identify (using receptor antagonist microinfusions into discrete brain regions) the critical sites in the CNS that might underlie this BDZ-opiate interaction. This work would represent the first systematic animal research on this phenomena and help to elucidate the precise nature and mechanisms underlying BDZ-opiate interactions.
