Intra-ventral tegmental area heroin-induced place preferences in rats are potentiated by peripherally administered alprazolam
Walker BM, Ettenberg A.
Behavioral Pharmacology Laboratory,
Department of Psychology,
University of California,
Santa Barbara, CA 93106, United States.
Pharmacol Biochem Behav. 2005 Nov;82(3):470-7.
ABSTRACTThe present experiment was designed to replicate and extend previous results of an opiate+benzodiazepine interaction in which peripherally administered alprazolam was observed to modulate behavior resulting from intravenous injections of heroin. As a first step in determining the role of central sites in this drug interaction, changes in drug reward (measured by conditioned place preference; CPP) were assessed in rats given systemic administration of alprazolam coupled with intracranially infused heroin (into the ventral tegmental area; VTA). Sprague-Dawley rats were implanted with guide cannula targeting the VTA, after which a heroin-induced CPP dose-response curve was determined (2.5-40 ng administered bilaterally in 0.5 microl/side). In other animals, intra-VTA heroin-induced place preferences were challenged with systemically applied alprazolam (0.125 mg/kg i.p.). The data confirm that rats dose-dependently develop reliable place preferences for a distinct environment paired with bilateral VTA-infusions of heroin. Additionally, when a non-rewarding dose of alprazolam was combined with a non-rewarding bilateral intra-VTA heroin dose (5 ng), a significant CPP was produced. These data extend earlier results by demonstrating that a systemically applied benzodiazepine can enhance the rewarding effects produced by central opiate administration. The results suggest that the VTA might be a site where this opiate+benzodiazepine interaction occurs.Xanax
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