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 μg/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 μg/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.