High levels of ethanol (EtOH) consumption during adolescence may be in part biologically driven, given that adolescents often manifest 2-3 fold greater EtOH intakes than adults in a variety of mammalian species. Studies in rats have suggested that such elevated intakes may be possible in part because adolescents are less sensitive than adults to aversive effects of EtOH and other intoxicating effects that may normally serve as cues to moderate intake. Genetic studies have found that sensitivity to aversive effects of EtOH plays an important role in moderating EtOH intake, and is more strongly related to EtOH intake than sensitivity to EtOH's rewarding properties. Despite compelling evidence for an association between insensitivity to EtOH aversion and enhanced EtOH intake, little is known about the ontogeny of these aversive sensitivities, their regional specificity and neural contributors. In conjunction with the DEARC NeuroCore and Animal/Behavior Core, the proposed work will address these critical gaps.
Aim 1 will use conditioned taste aversions (CTA) to examine the ontogeny of the developmental insensitivity to EtOH's aversive effects throughout the juvenile to adult period.
Aim 2 will assess c-Fos activation patterns to aversive effects of EtOH across age and associate these activation patterns with age differences in EtOH aversion. Focusing on an aversive region where activation is strongly linked to age differences in EtOH CTA, Aim 3 will determine whether reversible inactivation of that region diminishes age differences in EtOH's aversive effects and EtOH intake differences, while Aim 4 will examine potential neural substrates underlying the age differences in EtOH-induced activation in this region via examination of NMDA, GABA and opiate receptor regulation and intracellular signaling pathways.
Aim 5 will determine whether elevations in adolescent drinking induced by prenatal EtOH exposure are accompanied by exacerbated insensitivies to EtOH's aversive effects. Collectively, these studies will provide critical new information to further our understanding of how ontogenetic changes in the brain contribute to adolescent insensitivities to aversive properties of EtOH, and ultimately to the elevated levels of EtOH drinking characteristic of adolescence.
Adolescent alcohol use Is high, with adolescents across species ranging from humans to rodents often consuming 2-3 times more alcohol per occasion than adults. These elevated intakes appear related in part to an adolescent insensitivity to aversive effects of alcohol that seemingly serve to temper intake. This project assesses how the developing brain contributes to the resistance of adolescents to alcohol's aversive effects, information that may ultimately prove critical for reducing excessive adolescent alcohol use and later abuse.
|Russell, Ashley L; Tasker, Jeffrey G; Lucion, Aldo B et al. (2018) Factors promoting vulnerability to dysregulated stress reactivity and stress-related disease. J Neuroendocrinol 30:e12641|
|Mooney, Sandra M; Varlinskaya, Elena I (2018) Enhanced sensitivity to socially facilitating and anxiolytic effects of ethanol in adolescent Sprague Dawley rats following acute prenatal ethanol exposure. Alcohol 69:25-32|
|Lovelock, Dennis F; Deak, Terrence (2018) Neuroendocrine and neuroimmune adaptation to Chronic Escalating Distress (CED): A novel model of chronic stress. Neurobiol Stress 9:74-83|
|Barney, Thaddeus M; Vore, Andrew S; Gano, Anny et al. (2018) Assessment of Interleukin-6 Signaling Effects on Behavioral Changes Associated with Acute Alcohol Intoxication in adult male rats. Alcohol :|
|Surkin, P N; Brenhouse, H; Deak, T et al. (2018) Stress, alcohol and infection during early development: A brief review of common outcomes and mechanisms. J Neuroendocrinol 30:e12602|
|Doremus-Fitzwater, Tamara L; Paniccia, Jacqueline E; Gano, Anny et al. (2018) Differential effects of acute versus chronic stress on ethanol sensitivity: Evidence for interactions on both behavioral and neuroimmune outcomes. Brain Behav Immun 70:141-156|
|Diaz, Marvin Rafael; Przybysz, Kathryn Renee; Rouzer, Siara K (2018) Age as a factor in stress and alcohol interactions: A critical role for the kappa opioid system. Alcohol 72:9-18|
|Perkins, Amy E; Vore, Andrew S; Lovelock, Dennis et al. (2018) Late aging alters behavioral sensitivity to ethanol in a sex-specific manner in Fischer 344 rats. Pharmacol Biochem Behav 175:1-9|
|Akinmboni, T O; Davis, N L; Falck, A J et al. (2018) Excipient exposure in very low birth weight preterm neonates. J Perinatol 38:169-174|
|Varlinskaya, Elena I; Spear, Linda Patia; Diaz, Marvin R (2018) Stress alters social behavior and sensitivity to pharmacological activation of kappa opioid receptors in an age-specific manner in Sprague Dawley rats. Neurobiol Stress 9:124-132|
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