Ethanol use can lead to many potentially deleterious actions, such as drunk driving, increased aggression, and unprotected sex. One avenue by which ethanol may lead to these actions is by increasing impulsivity, as has been demonstrated in both animals and humans. No drugs are available that ameliorate ethanol's effects on impulsivity, and identifying such agents is difficult because ethanol has effects on several different receptors and regions in the brain. In addition, the mechanism of action of ethanol on impulsivity is not well understood. This is particularly true for delay discounting measures of impulsivity. Ethanol increases delay discounting (and thus increases impulsivity), but it is unknown whether this is due to an alteration in sensitivity to delays or in sensitivity to the magnitude of the reinforcers used in the task. Given that these sensitivities are associated with different neural circuits, disambiguating the effects of ethanol on these two circuits could provide valuable information about targets to block ethanol-induced impulsivity. Therefore, the overall goal of the proposed research is to better understand the neurological and behavioral basis of ethanol's effects on delay discounting by addressing the following specific aims.
Aim 1 will examine effects of ethanol on rats'performance in tasks designed to measure delay sensitivity and magnitude sensitivity independently. While the tasks themselves are not novel, this will be the first study to examine the effects of ethanol on delay sensitivity and magnitude sensitivity separately.
Aim 2 will examine the effect of ethanol on activity (indirectly measured via c-fos expression) in the brain regions of the task-associated circuits. Such information, coupled with the existing literature defining the circuits, will identify regions critical for ethanol's performance-altering effects.
Aim 3 will examine the effect of local inactivation of two of the brain regions in these circuits (expected: nucleus accumbens core and basolateral amygdala) to confirm their role in delay and magnitude sensitivity. If the specific aims are achieved, the proposed studies will lay the groundwork for future studies that systematically examine other regions of the delay and magnitude circuits and how drugs (including but not limited to ethanol) interact with them to increase impulsive behavior. Additional research may expand the examined circuitry to include other measures of impulsivity, as well as other factors (such as punishment contingencies or degree of effort required) that influence whether individuals initiate potentially deleterious actions.
Alcohol use increases impulsivity, which may lead to many potentially deleterious actions, such as drunk driving, increased aggression, and unprotected sex. Understanding the mechanisms underlying alcohol's effects on impulsivity would aid in developing a pharmacological treatment for these effects. This proposal seeks to determine the different neurological and behavioral mechanisms underlying the effects of alcohol on one form of impulsivity.
|Moschak, Travis M; Mitchell, Suzanne H (2014) Partial inactivation of nucleus accumbens core decreases delay discounting in rats without affecting sensitivity to delay or magnitude. Behav Brain Res 268:159-68|
|Tipps, Megan E; Moschak, Travis M; Mitchell, Suzanne H (2014) Behavioral disinhibition in mice bred for high drinking in the dark (HDID) and HS controls increases following ethanol. Drug Alcohol Depend 136:149-52|
|Helms, Christa M; McCracken, Aubrey D; Heichman, Sharon L et al. (2013) Ovarian hormones and the heterogeneous receptor mechanisms mediating the discriminative stimulus effects of ethanol in female rats. Behav Pharmacol 24:95-104|
|Moschak, Travis M; Mitchell, Suzanne H (2013) Sensitivity to reinforcer delay predicts ethanol's suppressant effects, but itself is unaffected by ethanol. Drug Alcohol Depend 132:22-8|
|Moschak, Travis M; Stang, Katherine A; Mitchell, Suzanne H (2013) Mice bred for severity of acute alcohol withdrawal respond differently in a go/no-go task. Alcohol Clin Exp Res 37:1483-90|