Social stress-escalated alcohol drinking, ventral tegmental area CRF-R1 antagonism, and accumbal dopamine in C57BL/6J mice.
Hwa, Lara.
2017-04-20T13:58:09.349Z
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Abstract: Excessive alcohol (EtOH) drinking is difficult to model in animals despite the extensive human literature demonstrating that stress increases EtOH consumption. The current experiments show escalations in voluntary EtOH drinking caused by a history of social defeat stress and intermittent access to EtOH in C57BL/6J mice compared to non-stressed mice given intermittent EtOH or continuous E... read moretOH. To explore a mechanistic link between stress and drinking, we studied the role of corticotropin-releasing factor type-1 receptors (CRF-R1) in the dopamine-rich ventral tegmental area (VTA). Intra-VTA infusions of a CRF-R1 antagonist, CP376395, infused into the VTA dose-dependently and selectively reduced intermittent EtOH intake in stressed and nonstressed mice, but not in mice given continuous EtOH. In contrast, intra-VTA infusions of the CRF-R2 antagonist astressin2B non-specifically suppressed both EtOH and H2O drinking in the stressed group without effects in the nonstressed mice. Using in vivo microdialysis in the nucleus accumbens, we observed that stressed mice drinking EtOH intermittently had elevated levels of tonic dopamine concentrations compared to non-stressed drinking mice. Also, VTA CP376395 potentiated dopamine output to the accumbens only in the stressed group causing further elevations of dopamine post-infusion. These findings illustrate a role for extrahypothalamic CRF-R1 as especially important for stress-escalated EtOH drinking beyond schedule-escalated EtOH drinking. CRF-R1 may be a mechanism for balancing the dysregulation of stress and reward in alcohol use disorders.
Thesis (Ph.D.)--Tufts University, 2015.
Submitted to the Dept. of Psychology.
Advisor: Klaus Miczek.
Committee: Joseph DeBold, Lisa Shin, and Kathleen Grant.
Keywords: Physiological psychology, Pharmacology, and Behavioral psychology.read less - ID:
- n87103205
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