DRUG DEPENDENCE LIABILITY OF TRICYCLIC ANTIDEPRESSANTS EVALUATED IN MONKEYS

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Abstract
Drug depenence liabilty of 5 tricyclic antidepressants, imipramine, imipramine-N-oxide, protriptyline, maprotiline and iprindole, were examined using rhesus monkeys. In gross behavioral observations of acute central nervous system effects in normal monkeys, imipramine, protriptyline, maprotiline and iprindole produced a decrease of awareness, mydriasis, ataxia, tremor and convulsions, but imipramine-N-oxide did not. In cross intravenous self-administration of the drugs with a standard stimulant and saline, no meaningful reinforcing effect on monkeys' drug-seeking behavior was observed with any drug, with the exception of one of the 4 monkeys with iprindole. In the continuous self-administration test, positive self-administration was observed in 2 out of 4 monkeys with imipramine and in one monkey each with imipramine-N-oxide, protriptylin and iprindole. But the self-administration rates were considerably low in comparison with that of principle drugs of abuse and none of these monkeys manifested observable drug effects. No monkey showed positive self-administration of maprotiline. Thus, the amphetamine-like dependence liability was not found in these drugs.

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