A pentylenetetrazol‐like stimulus during cocaine withdrawal: Blockade by diazepam but not haloperidol

Abstract

Abstract In the present experiment, rats were trained to discriminate the stimulus properties of an anxiogenic drug, pentylenetetrazol (PTZ), 20 mg/kg, from saline using a food‐rewarded two‐lever choice task. Following training, substitution tests were performed, and rats selected the PTZ‐appropriate lever after PTZ in a dose‐dependent manner. Cocaine (5–20 mg/kg) did not substitute for PTZ. Subsequently, testing and training were halted, and cocaine, 20 mg/kg/8 hr, was administered to three groups of ten rats per group for 3, 7, and 14 days. Withdrawal from cocaine produced a PTZ‐like stimulus that increased in intensity proportionally to the duration of chronic cocaine exposure. The selection of the PTZ lever by these subjects during withdrawal was reversed following administration of diazepam, 5 mg/kg, but not by haloperidol, 0.64 mg/kg. Stimulus control tests performed 2 weeks following the last withdrawal test demonstrated a return to baseline responding, with no significant loss of stimulus control. These data demonstrate the development of a PTZ‐like interoceptive stimulus during withdrawal from cocaine, which suggests the possibility of an anxiety‐like stimulus during cocaine withdrawal. This anxiety‐like component appears to be influenced by the duration of cocaine exposure.