Effects of monoamines on the intrinsic excitability of lateral orbitofrontal cortex neurons in alcohol-dependent and non-dependent female mice

NEUROPHARMACOLOGY

卷:137

Article

Nimitvilai, Sudarat¹  Lopez, Marcelo F.²  Woodward, John J.^1,2 

[1] Med Univ South Carolina, Dept Neurosci, 67 President St, Charleston, SC 29425 USA

[2] Med Univ South Carolina, Dept Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA

关键词: Chronic intermittent ethanol exposure;    Lateral orbitofrontal cortex;    Female mice;    Monoamine;    G protein-coupled inwardly rectifying;    potassium channel;    Intrinsic excitability;   

DOI  :  10.1016/j.neuropharm.2018.04.019

来源: Elsevier

【 摘 要 】

Changes in brain reward and control systems of frontal cortical areas including the orbitofrontal cortex (OFC) are associated with alcohol use disorders (AUD). The OFC is extensively innervated by monoamines, and drugs that target monoamine receptors have been used to treat a number of neuropsychiatric diseases, including AUDs. Recent findings from this laboratory demonstrate that D2, alpha 2-adrenergic and 5HT(1A) receptors all decrease the intrinsic excitability of lateral OFC (IOFC) neurons in nave male mice and that this effect is lost in mice exposed to repeated cycles of chronic intermittent ethanol (CIE) vapor. As biological sex differences may influence an individual's response to alcohol and contribute to the propensity to engage in addictive behaviors, we examined whether monoamines have similar effects on IOFC neurons in control and CIE exposed female mice. Dopamine, norepinephrine and serotonin all decreased spiking of IOFC neurons in naive females via activation of G(i alpha)-coupled D2, alpha 2-adrenergic and 5HT(1A) receptors, respectively. Firing was also inhibited by the direct GIRK channel activator ML297, while blocking these channels with barium eliminated the inhibitory actions of monoamines. Following CIE treatment, evoked spiking of IOFC neurons from female mice was significantly enhanced and monoamines and ML297 no longer inhibited firing. Unlike in male mice, the enhanced firing of neurons from CIE exposed female mice was not associated with changes in the after-hyperpolarization and the small-conductance potassium channel blocker apamin had no effect on current-evoked tail currents from either control or CIE exposed female mice. These results suggest that while CIE exposure alters monoamine regulation of OFC neuron firing similarly in males and female mice, there are sex-dependent differences in processes that regulate the intrinsic excitability of these neurons. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

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