Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala

Stacey L. Robinson, Nancy J. Alexander, Rebecca J. Bluett, Sachin Patel, Brian A. McCool*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-Arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol.

Original languageEnglish (US)
Pages (from-to)474-484
Number of pages11
JournalNeuropharmacology
Volume108
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Keywords

  • Anandamide
  • Basolateral amygdala
  • CB1
  • Dependence
  • Endogenous cannabinoid
  • Ethanol

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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