Social stress-escalated alcohol drinking, ventral tegmental area CRF-R1 antagonism, and accumbal dopamine in C57BL/6J mice.
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 ... read moreEtOH. 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
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