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Involvement of Inhibitory Receptors in Modulating Dopamine Signaling and Synaptic Activity Following Acute Ethanol Exposure in Striatal Subregions

Journal article
Authors Rhona B. C. Clarke
Bo Söderpalm
Amir Lotfi
Mia Ericson
Louise Adermark
Published in Alcoholism-Clinical and Experimental Research
Volume 39
Issue 12
Pages 2364-2374
ISSN 0145-6008
Publication year 2015
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 2364-2374
Language en
Links dx.doi.org/10.1111/acer.12895
Keywords Alcohol, Glycine Receptor, GABA(A) Receptor, Nucleus Accumbens Shell, Dorsolateral Striatum, ventral tegmental area, freely moving rats, nicotinic, acetylcholine-receptors, sensitive glycine receptors, in-vivo, microdialysis, brain reward system, nucleus-accumbens, basal ganglia, extracellular dopamine, mesolimbic dopamine, Substance Abuse
Subject categories Psychiatry, Neurochemistry

Abstract

Background: Alcohol acts on both inhibitory and excitatory receptor systems resulting in a net increase in dopamine output in the ventral striatum (nucleus accumbens [nAc]), which is implicated in drug reward. However, the dorsal striatum may also be involved in reward-related behaviors. The objectives of this study were to investigate the role of inhibitory receptors in modulating the acute effects of ethanol (EtOH) on dopamine release and synaptic activity in the shell region of the nAc (nAcS) and dorsolateral striatum (DLS). Methods: EtOH (300 mM) was administered via reversed microdialysis in the nAcS or DLS of Wistar rats following pretreatment with glycine or GABA(A) receptor antagonist strychnine and bicuculline, respectively. Dopamine content in dialysate samples was quantified using high-performance liquid chromatography. In addition, local field potential recordings were performed in the nAcS and DLS in slices from Wistar rats. Population spike (PS) amplitude was measured following treatment with EtOH (50 mM) in slices pretreated with strychnine or bicuculline. Results: Local EtOH increased dopamine levels in both regions, an effect that strychnine pretreatment inhibited in the nAcS. EtOH-induced increases in accumbal dopamine were not blocked by a low (5 mu M) concentration of bicuculline, but were inhibited by pretreatment with higher bicuculline concentrations. None of the antagonists administered in the DLS prevented the EtOH-induced dopamine increase. Field potential recordings in the nAcS showed that acute EtOH produced an increase in PS amplitude which was blocked by both strychnine and bicuculline. In the DLS, EtOH induced a decrease in PS amplitude which was not influenced by strychnine or bicuculline. Conclusions: The current results show that changes in striatal dopamine output and synaptic activity induced by acute EtOH administration are modulated by inhibitory receptors in a subregion-specific manner.

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