Withdrawal from chronic haloperidol substitutes for the pentylenetetrazol discriminative stimulus.
The present study was designed to examine withdrawal from a therapeutic, non abused drug, haloperidol. Rats were trained to discriminate the anxiogenic compound pentylenetetrazol (PTZ) from water in a two lever, food reinforced, drug discrimination procedure. Dose effect curves were then determined for PTZ and the antipsychotic drug, haloperidol (0.1-1 mg/kg). Haloperidol did not substitute for PTZ, even at a dose that decreased rates of responding to approximately 15% of control values. Rats were then treated chronically with either 1 or 2 mg/kg/day haloperidol while training was suspended. After 5 days of chronic haloperidol 4/6 animals in the 1 mg/kg/day group and 5/7 in the 2 mg/kg/day group chose the PTZ lever when tested 24-48 hours after the last haloperidol injection. Haloperidol, 1 or 2 mg/kg, did not reverse PTZ-lever responding. After an additional 5 days of chronic haloperidol, 3/6 rats in the 1 mg/kg/day group and 5/7 rats in the 2 mg/kg/day group responded on the PTZ lever 24 hours after the last injection, and this was reversed with the anxiolytic, chlordiazepoxide (3.2-5.6 mg/kg). The current findings indicate that there is an anxiogenic component to withdrawal from haloperidol. In psychotic patients, abrupt discontinuation of haloperidol results in nausea, vomiting and sweating, as well as a "relapse into psychosis" characterized by anxiety, depression and internal chaos (1). Interestingly, the authors caution that the so-called relapse into psychosis may simply be a sign of withdrawal. The current findings support their view and suggest that abrupt discontinuation of psychoactive therapeutic agents may result in anxiety.
Bronson
M E
ME
Auburn University School of Pharmacy, Dept. of Pharmacal Sciences, AL 36849-5503.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000009:adverse effects*; D010433:Pentylenetetrazole / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D006220:Haloperidol; D010433:Pentylenetetrazole