Behaviorally inactive doses of mianserin antagonize the suppressant effect of lysergic acid diethylamide on a fixed-ratio operant.
Male Sprague-Dawley rats were trained to respond for food reinforcement on a fixed-ratio 15 schedule. Low, behaviorally inactive, doses of mianserin (0.1-1.0 mg/kg) administered 30 min before the operant session antagonized the behavioral suppression induced by lysergic acid diethylamide (LSD; 50 micrograms/kg) administered immediately before the session. Mianserin (0.5-1.0 mg/kg) also partially antagonized the behavioral suppressant effects of higher doses of LSD. At a dose which suppressed behavior to 70% of control when administered alone, mianserin (10 mg/kg) did not antagonize the behavioral suppression induced by LSD (100-200 micrograms/kg). The data suggest that the suppression of operant behavior produced by mianserin may be the result of nonselective or multiple actions, or possibly the emergence of an LSD-type partial agonist property. Specificity of drug action as an antagonist apparently occurs at the behaviorally inactive, low doses of mianserin which may act through a selective blockade of serotonin receptors stimulated by LSD.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D003984:Dibenzazepines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008238:Lysergic Acid Diethylamide / Q000037:antagonists & inhibitors*; D008297:Male; D008803:Mianserin / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012054:Reinforcement, Psychology
D003984:Dibenzazepines; D009292:Narcotic Antagonists; D011985:Receptors, Serotonin; D008803:Mianserin; D008238:Lysergic Acid Diethylamide