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TC Napier, PE Simson and BS Givens
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois.
The ventral pallidum/substantia innominata (VP/SI) is an infracommissural extension of the dorsal globus pallidus (GP). Functional studies suggest that the VP/SI is indirectly influenced by dopamine (DA) via inputs from dopaminoceptive regions. However, recent anatomical evidence indicates a direct dopaminergic projection to the VP/SI, but the physiologic and pharmacologic consequences of this input have not been evaluated. Thus, the present study was designed to electrophysiologically characterize VP/SI neuronal responses to i.v. administered apomorphine (APO) and microiontophoretically applied DA. Because of similarities in circuitry and morphology, VP/SI responses were compared to those obtained from the GP. Single neurons recorded in vivo from rat VP/SI and GP exhibited similar electrophysiologic characteristics. The majority of the 50 neurons tested with APO demonstrated a dose-related increase in firing rate, with equivalent maximum responses and equivalent doses that produced half-maximal responding (ED50) for the two brain areas. APO generally was antagonized by haloperidol, indicating that the agonist was acting at dopaminergic receptors to produce the observed rate changes. From 212 neurons tested, it was determined that microiontophoretically applied DA altered neuronal firing throughout both regions. However, more DA- sensitive neurons were encountered in the GP than the VP/SI (75% vs. 42%, respectively). DA-induced rate increases and decreases were observed, with rate suppression occurring most frequently. The maximum response and the current that produced half-maximal responding were comparable for the two regions for both response directions. Systemic administration of antagonists revealed that pallidal responses to dopamine likely involve both the D1 and D2 receptor subtypes. These studies 1) demonstrate that the VP/SI is a functionally important dopaminoceptive brain region, and (2) confirm previous work regarding dopaminergic regulation of the GP. The similarities in pharmacologic profiles of responses by GP and VP/SI neurons to dopaminergic agents likely reflect comparable circuitries for the two regions. The differential responding to systemically administered DA agonists and locally applied DA implies that a combination of direct and indirect influences ultimately determines the impact that an activated dopaminergic system has on pallidal brain regions.
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