McDaid_2016_J.Neurosci_36_7768

Reference

Title : Ethanol-Induced Motor Impairment Mediated by Inhibition of alpha7 Nicotinic Receptors - McDaid_2016_J.Neurosci_36_7768
Author(s) : McDaid J , Abburi C , Wolfman SL , Gallagher K , McGehee DS
Ref : Journal of Neuroscience , 36 :7768 , 2016
Abstract :

Nicotine and ethanol (EtOH) are among the most widely co-abused substances, and nicotinic acetylcholine receptors (nAChRs) contribute to the behavioral effects of both drugs. Along with their role in addiction, nAChRs also contribute to motor control circuitry. The alpha7 nAChR subtype is highly expressed in the laterodorsal tegmental nucleus (LDTg), a brainstem cholinergic center that contributes to motor performance through its projections to thalamic motor relay centers, including the mediodorsal thalamus. We demonstrate that EtOH concentrations just above the legal limits for intoxication in humans can inhibit alpha7 nAChRs in LDTg neurons from rats. This EtOH-induced inhibition is mediated by a decrease in cAMP/PKA signaling. The alpha7 nAChR-positive allosteric modulator PNU120596 [N-(5-chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea], which interferes with receptor desensitization, completely eliminated EtOH modulation of these receptors. These data suggest that EtOH inhibits alpha7 responses through a PKA-dependent enhancement of receptor desensitization. EtOH also inhibited the effects of nicotine at presynaptic alpha7 nAChRs on glutamate terminals in the mediodorsal thalamus. In vivo administration of PNU120596 either into the cerebral ventricles or directly into the mediodorsal thalamus attenuated EtOH-induced motor impairment. Thus, alpha7 nAChRs are likely important mediators of the motor impairing effects of moderate EtOH consumption. SIGNIFICANCE STATEMENT: The motor-impairing effects of ethanol contribute to intoxication-related injury and death. Here we explore the cellular and neural circuit mechanisms underlying ethanol-induced motor impairment. Physiologically relevant concentrations of ethanol inhibit activity of a nicotinic receptor subtype that is expressed in brain areas associated with motor control. That receptor inhibition is mediated by decreased receptor phosphorylation, suggesting an indirect modulation of cell signaling pathways to achieve the physiological effects.

PubMedSearch : McDaid_2016_J.Neurosci_36_7768
PubMedID: 27445152

Related information

Citations formats

McDaid J, Abburi C, Wolfman SL, Gallagher K, McGehee DS (2016)
Ethanol-Induced Motor Impairment Mediated by Inhibition of alpha7 Nicotinic Receptors
Journal of Neuroscience 36 :7768

McDaid J, Abburi C, Wolfman SL, Gallagher K, McGehee DS (2016)
Journal of Neuroscience 36 :7768