Increased sensitivity to rate-altering and discriminative stimulus effects of morphine following continuous exposure to naltrexone. 1991

A M Young, and S R Mattox, and M D Doty
Department of Psychology, Wayne State University, Detroit, MI 48202.

Two experiments evaluated whether termination of a continuous infusion of naltrexone altered sensitivity to the rate-suppressing or discriminative stimulus effects of morphine in rats. An 8-day infusion of saline or doses of 3, 10, or 18 mg/kg/day naltrexone did not alter rates of lever pressing maintained under fixed-ratio 30 schedules of food delivery. A dose of 10 mg/kg day naltrexone produced insurmountable antagonism of the rate-suppressing and analgesic effects of morphine. The ED50 of morphine for rate suppression decreased by 2-fold 1 day after termination of the 8-day infusion of 10 or 18 mg/kg/day naltrexone. The ED50 of morphine returned to initial values within 8 days. Termination of infusion of either saline or 3 mg/kg/day naltrexone did not alter the ED50 of morphine. Changes in morphine stimulus control were evaluated in rats trained to discriminate saline and 3.2 mg/kg morphine under fixed-ratio 15 schedules of food delivery. The ED50 of morphine for stimulus control or rate suppression decreased by 2-fold 1 day after termination of an 8-day infusion of 18 mg/kg/day naltrexone. The ED50 of morphine for rate suppression returned to initial values within 3 days; that for stimulus control, within 5 days. Thus, termination of exposure to high doses of naltrexone produced brief changes in sensitivity to the rate-altering and discriminative stimulus effects of morphine that parallel reported changes in sensitivity to the analgesic and lethal effects of morphine.

UI MeSH Term Description Entries
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297 Male Males
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009271 Naltrexone Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. Antaxone,Celupan,EN-1639A,Nalorex,Naltrexone Hydrochloride,Nemexin,ReVia,Trexan,EN 1639A,EN1639A
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011930 Reaction Time The time from the onset of a stimulus until a response is observed. Response Latency,Response Speed,Response Time,Latency, Response,Reaction Times,Response Latencies,Response Times,Speed, Response,Speeds, Response
D012055 Reinforcement Schedule A schedule prescribing when the subject is to be reinforced or rewarded in terms of temporal interval in psychological experiments. The schedule may be continuous or intermittent. Reinforcement Schedules,Schedule, Reinforcement,Schedules, Reinforcement
D004192 Discrimination, Psychological Differential response to different stimuli. Discrimination, Psychology,Psychological Discrimination
D004193 Discrimination Learning Learning that is manifested in the ability to respond differentially to various stimuli. Discriminative Learning,Discrimination Learnings,Discriminative Learnings,Learning, Discrimination,Learning, Discriminative
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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