Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone

Abstract

Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5-0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals.

Figure 1

Transient increase in alcohol self-administration following corticosterone exposure (7 d in drinking water). a) Total responses on the alcohol-reinforced lever were significantly increased on the first session following corticosterone exposure (CORT; 300 µg/ml; 7 d; n=10) relative to Water controls (n=10) and relative to the baseline (B). Self-administration returned to levels similar to the Water group on the following sessions. b) On the first session following CORT exposure, cumulative alcohol lever responses in the CORT group were increased throughout the self-administration session, resulting in increased alcohol intake (inset). c) Plasma CORT levels after the first self-administration session following Water/CORT exposure were significantly decreased in the CORT group relative to the Water group and as compared to baseline confirming efficacy of the CORT exposure protocol. *signifies significant difference from Water group (p<0.05). +signifies significant difference from baseline. Values on graphs represent mean ± s.e.m.

Figure 2

Corticosterone exposure (7 d) does not alter sucrose self-administration. a) Total responses on the sucrose-reinforced lever were not altered following corticosterone exposure (CORT; 300 µg/ml; 7 d; n=12) relative to Water exposure. b) Cumulative sucrose lever responses on the first session following Water/CORT exposure did not differ between the groups throughout the self-administration session. c) Plasma CORT levels after the first self-administration session following Water/CORT exposure were significantly decreased in the CORT group relative to the Water group and as compared to baseline confirming efficacy of the CORT exposure protocol. *signifies significant difference from Water group (p<0.05). +signifies significant difference from baseline. Values on graphs represent mean ± s.e.m.

Figure 3

Blood alcohol concentration is not altered by CORT exposure (7 d). Blood alcohol concentration following 1 g/kg (IG) is not altered following the end of CORT exposure in rats with a history of alcohol self-administration (n=8/grp). Values on graphs represent mean ± s.e.m.

Figure 4

Inhibition of CORT synthesis by metyrapone does not alter alcohol self-administration. a) Metyrapone pretreatment (10 or 30 mg/kg, SC; n=9) did not alter total alcohol-paired lever responses, b) cumulative responses or c) alcohol intake relative to vehicle (0). d) Plasma CORT levels were significantly reduced by 30 mg/kg metyrapone consistent with the compound’s mechanism of action. *signifies significant difference from vehicle group (p<0.05). Values on graphs represent mean ± s.e.m.

Figure 5

Corticosterone exposure (7 d) does not alter locomotor activity in an open field. Distance traveled over time in the open field at the end of CORT exposure did not differ between the CORT group and the Water control group (n=6/group) in rats with a history of alcohol self-administration. Values on graphs represent mean ± s.e.m.