Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective
Year: 2017
Type: review
Abstract: Glutamate signaling in the brain is one of the most studied targets in the alcohol research field. Here, we report the current understanding of how the excitatory neurotransmitter glutamate, its receptors, and its transporters are involved in low, episodic, and heavy alcohol use. Specific animal behavior protocols can be used to assess these different drinking levels, including two-bottle choice, operant self-administration, drinking in the dark, the alcohol deprivation effect, intermittent access to alcohol, and chronic intermittent ethanol vapor inhalation. Importantly, these methods are not limited to a specific category, since they can be interchanged to assess different states in the development from low to heavy drinking. We encourage a circuit-based perspective beyond the classic mesolimbic-centric view, as multiple structures are dynamically engaged during the transition from positive- to negative-related reinforcement to drive alcohol drinking. During this shift from lower-level alcohol drinking to heavy alcohol use, there appears to be a shift from metabotropic glutamate receptor-dependent behaviors to N-methyl-D-aspartate receptor-related processes. Despite high efficacy of the glutamate-related pharmaceutical acamprosate in animal models of drinking, it is ineffective as treatment in the clinic. Therefore, research needs to focus on other promising glutamatergic compounds to reduce heavy drinking or mediate withdrawal symptoms or both.
Source: F1000Research
Authors: Lara Hwa, Joyce Besheer, Thomas Kash
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,350
Awards: Unbiased analysis of molecular and circuit targets of low dose alcohol, The impact of HPA axis dysregulation on the interoceptive effects of alcohol, Role of the Dopaminergic PAG projection to BNST in alcohol abuse, Core 1: Brain Circuit Validation Core, Role of the Dopaminergic PAG projection to BNST in alcohol abuse, Molecular and Circuit Pathogenesis of Alcohol Use Disorders, Molecular and Cellular Alcohol Research Training, Extended Amygdala Regulation of Dorsal Raphe Function in Ethanol Self-Administration, 5/8 INIA Stress and Chronic Alcohol Interactions: Probing brain circuits that regulate alcohol stress interactions
OpenAlex ID: W2602811693
