L-Dopa repairs deficits in locomotor and investigatory exploration produced by denervation of catecholamine terminal fields in the forebrain of rats.

In a previous study rats were shown to have decreased locomotor and investigatory exploration after bilateral microinjections of 6-hydroxydopamine into the anterolateral hypothalamus. These deficits correlate with the loss of catecholamine terminals in neocortical, limbic, and anteromedioventral striatal brain sites. To test whether this correlation was causal, central catecholamines were increased by the intraperitoneal administration of L-3,4-dihydroxyphenylalanine (L-dopa), 10--40 mg/kg) after inhibition of extracerebral L-amino acid decarboxylase. Such treatment repaired the deficits in locomotor exploration and investigation in 6-hydroxydopamine rats. Pretreatment with the catecholamine antagonist chlorpromazine (1--2 mg/kg) blocked the increase in locomotor exploration and investigation produced by L-dopa in 6-hydroxydopamine rats. The results suggest, but do not prove, that L-dopa produced these behavioral effects by increasing central catecholamines at the denervated catecholamine receptor sites in the forebrain. These data and the data from the previous study are complementary evidence for the hypothesis that forebrain catecholamine synaptic action is necessary for normal exploratory behavior.