Alprazolam and oxazepam block the cue-induced reinstatement of extinguished cocaine seeking in rats.

Author(s): Goeders NE, Clampitt DM, Keller C, Sharma M, Guerin GF

Affiliation(s): Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, P.O. Box 33932, 1501 Kings Highway, Shreveport, LA 71130, USA. ngoede@lsuhsc.edu

Publication date & source: 2009-01, Psychopharmacology (Berl)., 201(4):581-8. Epub 2008 Sep 17.

Publication type: Research Support, N.I.H., Extramural

RATIONALE: We have previously reported that pretreatment with benzodiazepines reduces intravenous cocaine self-administration in rats. OBJECTIVE: This experiment was designed to investigate whether or not benzodiazepines would also inhibit the reinstatement of cocaine seeking induced by the presentation of a conditioned reinforcer. MATERIALS AND METHODS: Adult male rats were implanted with jugular catheters and trained to self-administer cocaine (0.25 mg/kg/infusion) during daily 2-h sessions. During training, cocaine delivery was paired with the presentation of a tone and the illumination of a houselight. Once a stable baseline of cocaine self-administration was observed, lever pressing was extinguished to less than 20% of baseline rates. During reinstatement testing, responding resulted in the presentation of the conditioned reinforcer (i.e., the houselight and tone previously paired with self-administered cocaine). RESULTS: The response-contingent presentation of the conditioned reinforcer reliably reinstated cocaine seeking. Pretreatment with alprazolam (2 or 4 mg/kg, ip) or oxazepam (20 or 40 mg/kg, ip) reversed the conditioned reinforcer-induced reinstatement of extinguished cocaine-seeking behavior at doses that did not reliably affect the conditioned reinforcer-induced reinstatement of extinguished food seeking, suggesting that benzodiazepines may not have reduced reinstatement responding due to non-specific reductions in behavior. CONCLUSIONS: These data suggest that benzodiazepines may be useful in blocking the ability of environmental cues to stimulate cocaine seeking.