Norepinephrine uptake inhibitors as biochemically and behaviorally selective antagonists of the locomotor stimulation induced by indirectly acting sympathomimetic amines in mice

Publisher Website
Google Scholar
Abstract
Pretreatment with the selective noradrenergic uptake inhibitors nisoxetine and desipramine antagonized the locomotor stimulant effect of d-amphetamine without reducing the drug's stereotypy-inducing action. A similar antagonism was observed with imipramine but not with fluoxetine, a selective serotonin uptake inhibitor and structural analog of nisoxetine. The order of potency of antagonism was desipramine > nisoxetine > imipramine. Nisoxetine also selectively reduced the locomotor activity induced by maximally effective doses of cocaine, d-N-ethylamphetamine, and methylphenidate, but not that induced by morphine. Biochemically, nisoxetine blocked the selective reduction in cerebral cortical endogenous and 3H-norepinephrine produced by amphetamine without itself significantly altering either measure. These data support the involvement of norepinephrine in the locomotor stimulant action of indirectly acting sympathomimetic amines.