Journal
NEUROPSYCHOPHARMACOLOGY
Volume 41, Issue 7, Pages 1831-1840Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2015.353
Keywords
-
Categories
Funding
- National Institute on Alcohol Abuse and Alcoholism of the US National Institutes of Health [K22 AA021414]
- Division of Intramural Clinical and Biological Research of the NIAAA/NIH
- Integrative Neuroscience Initiative on Alcoholism of the NIAAA/NIH
Ask authors/readers for more resources
The dorsolateral striatum mediates habit formation, which is expedited by exposure to alcohol. Across species, alcohol exposure disinhibits the DLS by dampening GABAergic transmission onto this structure's principal medium spiny projection neurons (MSNs), providing a potential mechanistic basis for habitual alcohol drinking. However, the molecular and circuit components underlying this disinhibition remain unknown. To examine this, we used a combination of whole-cell patch-clamp recordings and optogenetics to demonstrate that ethanol potently depresses both MSN- and fast-spiking intemeuron (FSI)-MSN GABAergic synaptic transmission in the DLS. Concentrating on the powerfully inhibitory FSI-MSN synapse, we further show that acute exposure of ethanol (50 mM) to striatal slices activates delta opioid receptors that reside on FSI axon terminals and negatively couple to adenylyl cyclase to induce a long-term depression of GABA release onto both direct and indirect pathway MSNs. These findings elucidate a mechanism through which ethanol may globally disinhibit the DLS.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available