Withdrawal from morphine generalizes to a pentylenetetrazol stimulus.
Rats trained to discriminate pentylenetetrazol (PTZ) from saline in a two-lever food-reinforced operant task were given a three-day course of morphine, 15 to 45 mg/kg tid, ip. On the third day naloxone produced dose-dependent generalization to the PTZ stimulus, with 66% of subjects selecting the PTZ lever after the highest dose (0.32 mg/kg). Following termination of morphine injections, generalization of spontaneous withdrawal was tested. Approximately 50% of subjects selected the PTZ lever at 24 and 48 hrs after the last morphine, and by 96 hrs the percentage of subjects selecting the PTZ lever had dropped to 11%. Rats that chose the PTZ lever at 48 hrs were given diazepam, 5.0 mg/kg, which blocked the PTZ-like stimulus. These data demonstrate that morphine withdrawal produces a stimulus with PTZ-like characteristics which can be blocked by an anxiolytic, and they suggest that the PTZ discrimination may have general utility for investigating drug dependence and withdrawal in animals.
D000818:Animals; D004192:Discrimination, Psychological; D006801:Humans; D008297:Male; D009020:Morphine / Q000633:toxicity*; D009021:Morphine Dependence / Q000523:psychology; D010433:Pentylenetetrazole / Q000494:pharmacology*; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D009020:Morphine; D010433:Pentylenetetrazole