Endogenous dopamine can modulate inhibition of substantia nigra pars reticulata neurons elicited by GABA iontophoresis or striatal stimulation

Abstract

Previous reports from this laboratory have described an ability of iontophoretically applied dopamine to attenuate the inhibitory effects of iontophoresed GABA on neurons of the substantia nigra pars reticulata. This finding raised the question of whether endogenous dopamine, released from dendrites of neighboring pars compacta dopamine neurons, might act as a neuromodulator which diminishes the inhibition of pars reticulata neurons evoked by either GABA iontophoresis or electrical stimulation of the striatonigral GABAergic pathway. Extracellular, single-unit activity of pars reticulata neurons was recorded in male rats anesthetized with chloral hydrate. In one set of studies, d-amphetamine, a drug reported to release dopamine from nigral dendrites, was administered intravenously (1.6 mg/kg) during regular, intermittent iontophoretic pulses of GABA. As had been previously observed with iontophoresed dopamine, i.v. amphetamine significantly lessened the inhibition of reticulata neurons produced by GABA application. This change was reflected by a decrease in GABA's inhibitory potency by 22% relative to the control level of inhibition achieved prior to amphetamine administration. Amphetamine caused no decreases in GABA's effectiveness, however, in animals that had previously received treatments that depleted or destroyed nigral dopamine stores, i.e., in rats pretreated with reserpine and alpha- methyl-p-tyrosine, or in rats with 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway. In a second set of experiments, amphetamine or dopamine was delivered iontophoretically while monitoring the GABA-mediated (bicuculline-reversible) inhibition of reticulata neurons that can be elicited by striatal stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

GABA, Not Glutamate, Controls the Activity of Substantia Nigra Reticulata Neurons in Awake, Unrestrained Rats

“…This afferent organization gives GABA inhibition a major role in regulating SNr neuronal activity. Although our study confirms previous work (Waszczak and Walters, 1986;Celada et al, 1999) suggesting that GABA provides a strong inhibitory action on SNr neurons in awake, unrestrained animals, it also reveals that this action is greater in an anesthetized preparation. This difference is probably induced by trichloroethanol, the main metabolite of chloral hydrate and mediator of most of its anesthetic effect.…”

Selective D1 and D2 dopamine agonists differentially alter basal ganglia glucose utilization in rats with unilateral 6-hydroxydopamine substantia nigra lesions

“…It has been reported and its release attenuates the inhibition of SN, output neurons that SKF-38393 does not alter RCGU in naive animals (Palacios evoked by electrical stimulation of the striatonigral GABAergic and Wiederhold, 1985). By contrast, we report that adminispathway (Cheramy et al, 198 1;Waszczak and Walters, 1986).…”

The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway

“…Likewise, bicuculline prevented the reduction in VMTh GABA release induced by systemic methamphetamine (Mark et al, 2004). Alternatively, blockade of inhibitory GABA A receptors on (residual) nigral DA cells may lead to increased DA release (Westerink et al, 1992) and attenuation of the inhibitory control driven by GABA A receptors onto nigrothalamic GABAergic neurons (Waszczak and Walters, 1986), which may also result in attenuation of the antiakinetic effect of L-DOPA.…”