Behavioral effects of the highly selective serotonin releasing agent 5-methoxy-6-methyl-2aminoindan

The behavioral effects of 5-methoxy-6-mcthyl-2-aminoindan (MMAI) wcrc examined using the drug discrimination procedure and direct observation for classification of the characteristic syndrome induced by MMAI. The stimulus effects of MMAI were studied in 5 different groups of rats trained to discriminate MMAI (1.71 mg/kg; 8 /xM/kg), MDMA (3,4-methylcnedi-oxymethamphetamine; 1.75 mg/kg; 7.6 ~,M/kg), (+)-MBDB ((+)-N-methylamino-(1,3-benzodioxo-5-yl)-2-butanamine; 1.75 mg/kg; 7.18 /~M/kg), (+)-amphetamine (1 mg/kg; 5.4/xM/kg), or LSD ((+)-Iysergic acid diethylamide tartrate; 0.08 mg/kg; 186 nM/kg) from saline. In substitution tests in rats trained to discriminate MMAI from saline, all the compounds which fully mimicked MMAI were serotonin (5-hydroxytryptamine, 5-HT) releasing agents. This substitution is symmetrical for MDMA and (+)-MBDB. Nevertheless, the dose-response curve of MMAI is parallel to those of (+)-fenfluramine (m-trifluoromethyl-N-ethylamphetamine) and p-chloroamphetamine. The results also show that MMAI lacks amphetamine-like and LSD-like discriminative stimulus effects, suggesting that MMAI is neither a psychostimulant or a hallucinogen. Tests of the discriminabil-ity of MMAI after 5-HT depletion with the selective serotonin synthesis inhibitor, p-chlorophenylalanine (2 × 200 mg/kg i.p., pretreatment 72 h before test), showed only saline appropriate responding. Prolonged block (ca. 1 week) of the MMAI cue by p-chlorophenylalaninc further supports the conclusion that endogenous 5-HT is essential for MMAI discrimination. Fluoxctine (10 mg/kg) or paroxetine (2.5 mg/kg), both selective 5-HT uptake inhibitors, reduced the discriminability of MMAI to 40 % an