title: Protracted withdrawal: sensitization of the anxiogenic response to cocaine in rats concurrently treated with ethanol.
abstract: Rats were trained to respond on one lever following an injection of saline and the alternate lever after the anxiogenic drug pentylenetetrazol (PTZ 20 mg/kg), according to a fixed ratio (FR10) schedule of food reinforcement. The trained animals were then administered dependence-producing regimens of either cocaine (20 mg/kg, [IP], three times daily for 7 days) or ethanol (mixed 4.5% w/v with sweetened liquid diet given for 5 days). Separate groups of trained rats were given either subthreshold regimens of cocaine (20 mg/kg, IP, three times daily for 5 days), ethanol (2.25% w/v of the diet given for 5 days), or both. Additional groups were matched for control groups. After discontinuation of these regimens, rats were administered test injections of either saline or cocaine, and tested for elicitation of the PTZ-stimulus at selected intervals of withdrawal. After a saline injection, maximum elicitation of the PTZ-stimulus was observed 12 hours following chronic treatment with the higher dose of ethanol, and 120 hours following longer treatment with cocaine. During those periods of withdrawal when a saline injection failed to produce a PTZ-like stimulus, a test injection of cocaine (10 mg/kg) elicited the PTZ-stimulus in the ethanol withdrawn rats, although only partially eliciting the PTZ-stimulus in the cocaine withdrawn group. In the pair-fed controls, or rats withdrawn from the smaller dosage of either ethanol or cocaine, the test dose of saline or cocaine did not elicit the PTZ-stimulus; only 30% of rats selected the PTZ-appropriate level at the highest dose of cocaine tested (10 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Texas College of Osteopathic Medicine, Fort Worth 76107.
authors.forename: P L
authors.initials: PL
authors.lastname: Prather
authors.forename: H
authors.initials: H
authors.lastname: Lal
mesh_terms: D000437:Alcoholism / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000523:psychology; D003042:Cocaine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D019966:Substance-Related Disorders / Q000523:psychology
chemical_list: D000431:Ethanol; D003042:Cocaine; D010433:Pentylenetetrazole