Intra-ventral tegmental area heroin-induced place preferences in rats are potentiated by peripherally administered alprazolam.
The 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.
Walker
Brendan M
BM
Behavioral Pharmacology Laboratory, Department of Psychology, University of California, Santa Barbara, CA 93106, United States.
Ettenberg
Aaron
A
D000525:Alprazolam / Q000494:pharmacology*; D000818:Animals; D003214:Conditioning, Classical; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D003932:Heroin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects*
D003932:Heroin; D000525:Alprazolam