Effects of lithium dose (UCS) on the acquisition and extinction of a discriminated morphine aversion: tests with morphine and delta9-THC.
The effects of varying the lithium dose (unconditioned stimulus [UCS]; LiCl range 30-180 mg/kg) on the acquisition and extinction of stimulus control by 5.6 mg/kg of morphine in a discriminated taste aversion (DTA) procedure were examined in rats. In addition, pharmacological specificity was examined by substituting (-)-delta-9-tetrahydrocannabinol (delta9-THC) for morphine during a test phase intervening between acquisition and extinction. DTA acquisition was more rapid at higher LiCl doses. The lowest dose of LiCl, 30 mg/kg, did not robustly maintain a DTA. Two groups treated with 60 mg/kg LiCl, differing only in the type of drinking nozzle used (ball-bearing vs standard non-ball-bearing), behaved similarly. Suppression of drinking was related to the morphine dose, in an orderly manner (dose range 0.3-10 mg/kg), in rats for which morphine was followed by LiCl. No significant decline in drinking occurred for rats for which morphine was followed by saline, except perhaps at the 10 mg/kg test dose of morphine. The control of drinking was pharmacologically specific; both experimental and control animals were equally affected in tests with delta9-THC (0.3-10 mg/kg). Low doses of delta9-THC increased water consumption; this did not occur with morphine. During extinction the reinstitution of drinking was similar across groups that had been effectively conditioned, i.e. there was no apparent effect of lithium dose on extinction. After extinction, a much attenuated reaction occurred to morphine in tests with 3 and 10 mg/kg. These doses of morphine had significantly suppressed drinking before the extinction phase. Collectively, these data add to the formal similarities between sensory and drug discriminative stimuli.
Järbe
T U
TU
Department of Psychiatry, MCP Hahnemann University, Philadelphia, Pennsylvania, USA.
Lamb
R J
RJ
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects*; D006213:Hallucinogens / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D018021:Lithium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006213:Hallucinogens; D009294:Narcotics; D009020:Morphine; D013759:Dronabinol; D018021:Lithium Chloride