Article

The effects of repeated corticosterone exposure on the interoceptive effects of alcohol in rats

Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building, CB#7178, Chapel Hill, NC 27599, USA.
Psychopharmacology (Impact Factor: 3.88). 10/2011; 220(4):809-22. DOI: 10.1007/s00213-011-2533-8
Source: PubMed

ABSTRACT

Repeated and/or heightened elevations in glucocorticoids (e.g., repeated stress) can promote escalated drug-taking behaviors and induce compromised HPA axis function. Given that interoceptive/subjective drug cues are a fundamental factor in drug-taking behavior, we sought to determine the effects of exposure to repeated elevations in the glucocorticoid corticosterone (CORT) on the interoceptive effects of alcohol in rats using drug discrimination techniques.
Male Long Evans rats trained to discriminate alcohol (1 g/kg, IG) vs. water were exposed to CORT (300 μg/ml) in the home cage drinking water for 7 days. The interoceptive effects of experimenter- and self-administered alcohol were assessed and HPA axis function was determined.
The interoceptive effects of experimenter- and self-administered alcohol were blunted following CORT. Control experiments determined that this decreased sensitivity was unrelated to discrimination performance impairments or decreased CORT levels at the time of testing and was dependent on repeated CORT exposure. Susceptibility to compromised HPA axis function following CORT exposure was suggested by an altered pattern of CORT secretion and blunted CORT response following injection of the synthetic glucocorticoid dexamethasone.
These findings present a possible behavioral mechanism for escalated alcohol drinking during episodes of heightened elevations in glucocorticoids (e.g., stress). That is, during these episodes, individuals may consume more alcohol to achieve the desired interoceptive effects. Understanding these behavioral mechanisms may lead to a better understanding of factors that promote alcoholism and alcohol abuse in at risk populations.

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    • "Chronic corticosterone exposure in rats also can reduce sensitivity to the subjective (i.e., discriminative stimulus) effects of alcohol (Besheer et al. 2012). A similar outcome also has been reported following chronic alcohol exposure and withdrawal in mice (Becker and Baros 2006). "
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    ABSTRACT: A complex relationship exists between alcohol-drinking behavior and stress. Alcohol has anxiety-reducing properties and can relieve stress, while at the same time acting as a stressor and activating the body's stress response systems. In particular, chronic alcohol exposure and withdrawal can profoundly disturb the function of the body's neuroendocrine stress response system, the hypothalamic-pituitary-adrenocortical (HPA) axis. A hormone, corticotropin-releasing factor (CRF), which is produced and released from the hypothalamus and activates the pituitary in response to stress, plays a central role in the relationship between stress and alcohol dependence and withdrawal. Chronic alcohol exposure and withdrawal lead to changes in CRF activity both within the HPA axis and in extrahypothalamic brain sites. This may mediate the emergence of certain withdrawal symptoms, which in turn influence the susceptibility to relapse. Alcohol-related dysregulation of the HPA axis and altered CRF activity within brain stress-reward circuitry also may play a role in the escalation of alcohol consumption in alcohol-dependent individuals. Numerous mechanisms have been suggested to contribute to the relationship between alcohol dependence, stress, and drinking behavior. These include the stress hormones released by the adrenal glands in response to HPA axis activation (i.e., corticosteroids), neuromodulators known as neuroactive steroids, CRF, the neurotransmitter norepinephrine, and other stress-related molecules.
    Preview · Article · Mar 2012 · Alcohol research : current reviews
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    • "The higher ingestion of EtOH by Dom compared to Sdom rats may also have been influenced by a change in interoceptive properties of the drug. For example, psychosocial stress may alter the salience and/or the rewarding properties of drugs (Vekovischeva et al., 2004), and repeated exposure to elevated CORT levels, consequent to daily confrontations, may have altered sensitivity to the interoceptive effects of alcohol in rats (Besheer et al., 2011) and induced the Dom animals to consume more EtOH. Therefore, one may speculated that while at the pre-dyad test the future Dom rats tended to experienced less reward from ingesting EtOH's compared to the future Sdom rats, on the other hand at the dyad test the Sdom rats may have found EtOH more aversive (Rezvani et al., 2010). "
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  • [Show abstract] [Hide abstract]
    ABSTRACT: A complex relationship exists between alcohol-drinking behavior and stress. Alcoholhas anxiety-reducing properties and can relieve stress, while at the same time actingas a stressor and activating the body's stress response systems. In particular, chronicalcohol exposure and withdrawal can profoundly disturb the function of the body'sneuroendocrine stress response system, the hypothalamic-pituitary-adrenocortical(HPA) axis. A hormone, corticotropin-releasing factor (CRF), which is produced andreleased from the hypothalamus and activates the pituitary in response to stress, playsa central role in the relationship between stress and alcohol dependence andwithdrawal. Chronic alcohol exposure and withdrawal lead to changes in CRF activityboth within the HPA axis and in extrahypothalamic brain sites. This may mediate theemergence of certain withdrawal symptoms, which in turn influence the susceptibilityto relapse. Alcohol-related dysregulation of the HPA axis and altered CRF activity withinbrain stress-reward circuitry also may play a role in the escalation of alcoholconsumption in alcohol-dependent individuals. Numerous mechanisms have beensuggested to contribute to the relationship between alcohol dependence, stress, anddrinking behavior. These include the stress hormones released by the adrenal glandsin response to HPA axis activation (i.e., corticosteroids), neuromodulators known asneuroactive steroids, CRF, the neurotransmitter norepinephrine, and other stress-related molecules.
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