The behavioral as well as neurochemical effects of long-term administration of the tricyclic antidepressant desipramine and the selective monoamine oxidase (MAO) type A-inhibiting antidepressant clorgyline were studied in rats. As previously observed with clorgyline, long-term but not short-term desipramine administration attenuated the suppressant effect of clonidine on self-stimulation behavior, demonstrating adaptive changes in the noradrenergic system with both antidepressants. Failure of long-term clorgyline treatment to down-regulate alpha 1, alpha 2 and beta-adrenergic receptor densities in 6-hydroxydopamine lesioned animals further demonstrates that adrenergic receptor adaptation to MAO inhibitors is a response to an increase in catecholamine receptor occupancy. In another study, continuous administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) via osmotic minipumps to rats was shown to produce sustained locomotor deficits which might be related to the movement disorders (akinesia) of Parkinson's disease.