Abstract
The past two decades of data derived from addicted individuals and preclinical animal models of addiction implicate a role for the excitatory glutamatergic transmission within the mesolimbic structures in alcoholism. The cellular localization of the glutamatergic receptor subtypes, as well as their signaling efficiency and function, are highly dependent upon discrete functional constituents of the postsynaptic density, including the Homer family of scaffolding proteins. The consequences of repeated alcohol administration on the expression of the Homer family proteins demonstrate a crucial and active role, particularly for the expression of Homer2 isoform, in regulating alcohol-induced behavioral and cellular neuroplasticity. The interaction between Homer2 and alcohol can be defined as a mutual relation: alcohol consumption enhances the expression of Homer2 protein isoform within the nucleus accumbens and the extended amygdala, cerebral areas where, in turn, Homer2 is able to mediate the development of the “pro-alcoholic” behavioral phenotype, as a consequence of the morpho-functional synaptic adaptations. Such findings are relevant for the detection of the strategic molecular components that prompt alcohol-induced functional and behavioral disarrangement as targets for future innovative treatment options.
Highlights
Chronic and excessive alcohol consumption is associated with several neuropsychiatric effects, such as impairment in judgment, learning, memory, perception, and motor coordination [1, 2] characterized by aberrant morpho-functional plasticity at the synaptic level [3]
This review summarizes the physiological role played by Homer proteins as a whole, with an emphasis on the most recent evidence on Homer2 isoforms
The interaction between Homer2 and alcohol can be defined as a mutual relation: alcohol consumption enhances Homer2 protein isoforms expression within NAC and the extended Amy, cerebral areas where, in turn, Homer2 is able to mediate alcohol rewarding properties, leading to further alcohol consumption
Summary
Chronic and excessive alcohol consumption is associated with several neuropsychiatric effects, such as impairment in judgment, learning, memory, perception, and motor coordination [1, 2] characterized by aberrant morpho-functional plasticity at the synaptic level [3]. It is possible to theorize that an alcohol-induced increase in Homer signaling and, in glutamate receptor plasticity, within both the “motor” (NACc) and “motive” (NACsh) striatal regions, and in ceAmy, is a pharmacodynamic response to alcohol that likely contributes to the propensity to further consume excessive amounts of alcohol [44, 84] (Table 1) In this regard, converging data derived from both human [51] and animal [44, 47,48,49,50] studies implicate Homer gene products in behavioral sensitivity to alcohol and addiction vulnerability. Homer2b overexpression elevates, while Homer2b knockdown reduces alcohol intake in both lines in a
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
