Synaptic effects of ethanol on striatal circuitry: therapeutic implications for dystonia

Abstract

Alcohol consumption affects motor behavior and motor control. Both acute and chronic alcohol abuse have been extensively investigated, however the therapeutic efficacy of alcohol on some movement disorders, such as myoclonus-dystonia or essential tremor, still does not have a plausible mechanistic explanation. Yet, there are surprisingly few systematic trials with known GABAergic drugs mimicking the effect of alcohol on neurotransmission. In this brief survey, we aim to summarize the effects of ethanol (EtOH) on striatal function, providing an overview of its cellular and synaptic actions in a "circuitcentered" view. In addition, we will review both experimental and clinical evidence, in the attempt to provide a plausible mechanistic explanation for alcohol-responsive movement disorders, with particular emphasis on dystonia. Different hypotheses emerge, which may provide a rationale for the utilization of drugs that mimic alcohol effects, predicting potential drug repositioning.

The pathogenesis of blepharospasm

“…Anxiety and depression were identified as independent risk factors of blepharospasm. Conversely, smoking, alcohol consumption, and coffee consumption may reduce the risk of developing blepharospasm ( 21 , 22 ). A multicenter case–control study in Italy showed that coffee consumption was negatively correlated with the risk of primary blepharospasm, and that the intensity of this association increased with an increase in the average number of cups of coffee per day ( 23 ).…”

Synaptic Dysfunction in Dystonia: Update From Experimental Models

“…In addition, SGCE, by mediating the link between the cytoskeleton and the extracellular matrix, influences the morphology of dopaminergic neurons [ 135 ]. As discussed in a recent review, alcohol could exert its beneficial effects in DYT11 by modulating the output from the dorsal striatum and, in turn, motor control [ 139 ]. In more detail, alcohol may act on the dopaminergic system and striatal LTD induction either directly or indirectly, through the endocannabinoid system [ 140 ].…”