Differential effects of nitric oxide synthase inhibitor, 7-nitroindazole, on discriminative stimulus and somatic effects of naloxone in morphine-dependent rats.
Our previous report suggested that antagonists acting at NMDA receptors attenuate discriminative stimulus effects of naloxone in morphine dependent rats. Nitric oxide (NO) is a putative second messenger which mediates NMDA receptor activation. The present study evaluated behavioral effects of NO synthase inhibitor, 7-nitroindazole in morphine-dependent rats trained to discriminate 0.1 mg/kg naloxone from saline. 7-Nitroindazole did not significantly affect naloxone's discriminative stimulus effects but decreased naloxone-induced weight loss and abolished expression of several withdrawal signs--diarrhea, scream on touch, tremor and 'wet dog'-like shaking suggesting different mechanisms for subjective and somatic components of opioid withdrawal.
Medvedev
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Laboratory of Behavioral Pharmacology, Valdman Institute of Pharmacology, Pavlov Medical University, St. Petersburg, Russia.
Dravolina
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Bespalov
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D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D019966:Substance-Related Disorders / Q000209:etiology
D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D007191:Indazoles; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole