High stress levels are believed to be a risk factor for ethanol abuse in humans, and the excessive intake of ethanol is associated with increased measures of stress. This analysis addresses longitudinal changes in basal (resting) hypothalamic-pituitary-adrenal (HPA) axis activity as a function of ethanol self-administration in cynomolgus monkeys. Previous findings indicate that pre-ethanol endocrine response to dexamethasone challenge is correlated with subsequent ethanol intake, but the basal state had not yet been examined. The first cohort of male monkeys (n = 10) have completed the timeline of the experiment. This analysis looks at their basal HPA axis function over four time points: before exposure to ethanol, after ethanol induction, after six months of self-administration, and after twelve months of self-administration. The basal measures of HPA axis function were blood levels of ACTH, cortisol, and DOC measured at 15, 30, 60, 90, and 120 minutes after an injection of saline. Peak and Area Under the Curve (AUC) values were calculated and compared. As expected, peak and AUC values were highly correlated at every time point. ACTH levels were significantly higher after induction compared to before induction (p < 0.0005). They continued to increase under self-administration and were significantly higher after 12 months compared to after induction (p = 0.013). Cortisol levels remained unchanged over time. DOC levels increased after ethanol induction (p = 0.001) and again after twelve months of self-administration (p = 0.002). After twelve months of self-administration, basal ACTH levels were highly correlated with average daily intake (Peak: R-squared=0.81, p < 0.0005; AUC: R-squared=0.65, p < 0.005). No such correlation was found with cortisol or DOC measurements. With only one cohort, there was insufficient power to determine if pre-alcohol basal HPA axis measures can predict future ethanol intake. These data show that hormonal measures of basal stress increase proportionally with ethanol intake. In contrast to pre-ethanol response to a dexamethasone challenge, there is insufficient evidence at this time to suggest that pre-alcohol basal (resting) stress levels can predict future ethanol intake. (Funded by U01 AA13510.)
Stress and ethanol self-administration in monkeys: Basal measures of HPA axis activity as a function of ethanol intake over time
Porcu P;
2007
Abstract
High stress levels are believed to be a risk factor for ethanol abuse in humans, and the excessive intake of ethanol is associated with increased measures of stress. This analysis addresses longitudinal changes in basal (resting) hypothalamic-pituitary-adrenal (HPA) axis activity as a function of ethanol self-administration in cynomolgus monkeys. Previous findings indicate that pre-ethanol endocrine response to dexamethasone challenge is correlated with subsequent ethanol intake, but the basal state had not yet been examined. The first cohort of male monkeys (n = 10) have completed the timeline of the experiment. This analysis looks at their basal HPA axis function over four time points: before exposure to ethanol, after ethanol induction, after six months of self-administration, and after twelve months of self-administration. The basal measures of HPA axis function were blood levels of ACTH, cortisol, and DOC measured at 15, 30, 60, 90, and 120 minutes after an injection of saline. Peak and Area Under the Curve (AUC) values were calculated and compared. As expected, peak and AUC values were highly correlated at every time point. ACTH levels were significantly higher after induction compared to before induction (p < 0.0005). They continued to increase under self-administration and were significantly higher after 12 months compared to after induction (p = 0.013). Cortisol levels remained unchanged over time. DOC levels increased after ethanol induction (p = 0.001) and again after twelve months of self-administration (p = 0.002). After twelve months of self-administration, basal ACTH levels were highly correlated with average daily intake (Peak: R-squared=0.81, p < 0.0005; AUC: R-squared=0.65, p < 0.005). No such correlation was found with cortisol or DOC measurements. With only one cohort, there was insufficient power to determine if pre-alcohol basal HPA axis measures can predict future ethanol intake. These data show that hormonal measures of basal stress increase proportionally with ethanol intake. In contrast to pre-ethanol response to a dexamethasone challenge, there is insufficient evidence at this time to suggest that pre-alcohol basal (resting) stress levels can predict future ethanol intake. (Funded by U01 AA13510.)I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
