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

Abstract

We have previously reported that pretreatment with benzodiazepines reduces intravenous cocaine self-administration in rats. 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. 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). 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. These data suggest that benzodiazepines may be useful in blocking the ability of environmental cues to stimulate cocaine seeking.