ALTERATIONS IN STRIATAL NEUROTROPHIC ACTIVITY-INDUCED BY DOPAMINERGIDDRUGS

The administration of dopaminergic drugs induces a variety of compensa tory responses ostensibly designed to reinstate normal dopamine (DA) t one. We have hypothesized that drug-induced alterations in striatal-de rived neurotrophic activity contributes to these compensatory processe s. This phenomenon has been studied by examining the growth of mesence phalic cultures incubated with cell-free extracts of striatal tissue t aken from patients or rats treated with various drugs. Our results rev eal that reducing striatal DA tone by administering the DA antagonist haloperidol, the DA neurotoxin 6-hydroxydopamine, or as occurs natural ly in Parkinson's disease, increases striatal trophic activity. Conver sely, increasing striatal DA tone by administering the indirect DA ago nists amphetamine or levodopa reduces trophic activity in the striatum . Kainic acid lesions of the striatum similarly reduce this trophic ac tivity. The implications of these drug-induced alterations in trophic activity are discussed and reviewed.