Long-term influence of an initial exposure to alcohol on the rat hypothalamic-pituitary axis

Objective: We have previously shown that adult male rats injected with alcohol daily for 3 consecutive days displayed a significantly blunted ACTH to a second alcohol injection, given 3 to 7 days later. The purpose of the present work was to determine the maximum duration over which the ACTH response remained blunted after an initial alcohol treatment. Methods: Male rats were exposed to alcohol (intragastrically or via vapors for 4 hr) on three consecutive days, starting when they were 22 (group A), 34 (group B), or 50 days old (group C). Control animals were injected with the vehicle intragastrically or kept in chambers through which normal air was circulated. At 60 days of age, the animals were injected with the vehicle or alcohol (4.5 g/kg intragastrically) to determine whether the initial treatment had long-term consequences on the ACTH response to a second alcohol challenge. Results: Rats of group C, pretreated with alcohol via intragastric injections or vapors, all exhibited a blunted ACTH response to the second acute alcohol challenge. In contrast, the second alcohol challenge only attenuated ACTH responses in rats of group B that had received intragastric injections, but not vapors. Group A showed a comparable response to acute intragastric alcohol injection at 60 days of age regardless of whether they had been preexposed to the drug. This was not due to a lack of neuroendocrine response because alcohol vapors significantly increased plasma ACTH levels and up-regulated paraventricular nucleus neuronal activity regardless of the age at which it was initially administered. Conclusions: Repeated (daily for 3 consecutive days) administration of alcohol by the gastric route induces a long-lasting (up to 24 days) but not permanent blunting of the ACTH response to a second (acute) alcohol challenge. The fact that alcohol delivered by inhalation only caused a relatively brief (less than or equal to8 days) decrease in the ability of a second intragastric alcohol challenge to release ACTH suggests that the mode of alcohol delivery influences its long-term consequences.