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J Neurosci. 2002 Feb 15;22(4):1407-13.

Distinct roles for nigral GABA and glutamate receptors in the regulation of dendritic dopamine release under normal conditions and in response to systemic haloperidol.

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1
Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102, USA. cobb@axon.rutgers.edu

Abstract

The regulation of dendritic dopamine release in the substantia nigra (SN) likely involves multiple mechanisms. GABA and glutamate inputs to nigrostriatal dopamine neurons exert powerful influences on dopamine neuron physiology; therefore, it is probable that GABA and glutamate likewise influence dendritic dopamine release, at least under some conditions. The present studies used in vivo microdialysis to determine the potential roles of nigral GABA and glutamate receptors in the regulation of dendritic dopamine release under normal conditions and when dopamine signaling in the basal ganglia is compromised after systemic haloperidol administration. Nigral application of the GABA(A) receptor antagonist bicuculline by reverse dialysis significantly increased spontaneous dopamine efflux in the SN. However, spontaneous dopamine efflux in the SN was not significantly affected by local application of the glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione or (+/-)-3-[2-carboxypiperazine-4-yl]-propyl-1-phosphonic acid. Systemic haloperidol administration significantly increased the extracellular dopamine measured in the SN. Blockade of nigral GABA(A) receptors by local bicuculline application did not alter this effect of systemic haloperidol, despite the bicuculline-induced increase in spontaneous dendritic dopamine efflux. In contrast, nigral application of either glutamate receptor antagonist significantly attenuated the increases in dendritic dopamine efflux elicited by systemic haloperidol. These data suggest that under normal conditions, activity of GABA afferents to SN dopamine neurons is an important determinant of the spontaneous level of dendritic dopamine release. Circuit-level changes in the basal ganglia involving an increased glutamatergic drive to the SN appear to underlie the increase in dendritic dopamine release that occurs in response to systemic haloperidol administration.

PMID:
11850467
[Indexed for MEDLINE]
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