Biochemical and behavioral evaluation of pergolide as a dopamine agonist in the rat brain

The ergot derivative pergolide was evaluated as a dopamine agonist using various behavioral and biochemical analyses. Spontaneous motor activity was decreased by small doses (0.1 mg/kg) of pergolide and increased with larger doses (above 0.5 mg/kg). Hypermotility after larger doses persisted for as long as 24 hr and was succeeded by a period of hypomotility. The doses of drug, sufficient to produce hypermotility, also produced stereotypy. With repeated daily injections (2 weeks), the period of hypermotility decreased and the ensuing period of hypomotility increased. Stereotyped behavior was similarly affected. Chronic administration of pergolide did not alter the magnitude of the behavioral responses. Levels of the dopamine (DA) metabolites, dihydroxyphenylacetate (DOPAC) and homovanillic acid (HVA), in the striatum and mesolimbic regions were decreased during the periods of hypermotility but returned to control levels during subsequent hypomotility. Activation of putative inhibitory presynaptic dopamine receptors by pergolide was studied by following accumulation of DOPA in rats treated with the dopamine neuron inhibiting agent, gamma-butyrolactone (GBL) and a DOPA-decarboxylase inhibitor. Pergolide significantly inhibited both striatal and mesolimbic accumulation of DOPA. In contrast, with changes in behavioral and metabolic indices, pergolide-induced inhibition of tyrosine hydroxylase was not affected by chronic treatment with pergolide. On the basis of both behavioral and biochemical data it is proposed that pergolide acts as a dopamine agonist with particularly long-lasting effects.