Excitation of type II caudate neurons by systemic administration of dopamine agonists

Using chloral hydrate anesthetized rats, dopamine (DA) agonists were evaluated for their systemic effects on firing rates of DA neurons in rat substantia nigra pars compacta (SNPC) and postsynaptic type II neurons in the anterior caudate nucleus (CN), the major projection area for SNPC DA neurons. Intravenous injections of the indirect DA agonist D-amphetamine, but not L-amphetamine, excited spontaneously active CN neurons by a haloperidol-sensitive mechanism. Doses to achieve CN excitation were similar to those required to inhibit SNPC firing. This data is consistent with the theory that D-amphetamine inhibition of SNPC DA neurons is dependent upon neuronal negative feedback pathways originating in CN. Intravenous injections of direct agonists apomorphine, which stimulates all DA receptor subtypes, and quinpirole, which only stimulates D2 receptor subtypes, increased firing rates of spontaneously active CN neurons, but only at doses above those inhibiting firing rates of SNPC neurons. SKF 38393, a selective D1 agonist, had little or no effect on the firing rates of DA neurons in SNPC, on type II anterior CN neurons, or on the effects of quinpirole on anterior CN neurons. It is concluded that excitation of type II anterior CN neurons is mediated via receptors of the D2 subfamily. These results are compared to those reported elsewhere for type I CN neurons, and the possible relevance of these results for the role of DA in motor function is discussed.