Serotonin and serotonin 1-A receptors in the failure of ethanol-treated rats to adapt to a repeated stress schedule.

Objective: The effects of repeated-restraint stress on brain 5-hydroxytryptamine; serotonin (5-HT) metabolism and functional responses to a selective 5-HT-1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), are compared in water- and ethanol-treated rats.

Method: Locally bred male water- or ethanol-treated rats restrained 2 hours per day for 6 days were killed, and whole brains were collected for the neurochemical analysis by high performance liquid chromatography with electrochemical detection (HPLC-EC). In a separate experiment 8-OH-DPAT was injected in water- and ethanol-treated rats to compare elicited hyperactivity syndrome (a postsynaptic response) and effectiveness of the drug in reducing brain 5-HT synthesis (a presynaptic response).

Results: A single episode of 2-hour restraint stress decreased 24-hour cumulative food intake in both water- and ethanol-treated rats. Following repeated restraint stress of 2 hours per day for 5 days, the decreases were present in ethanol- but not water-treated rats. The sixth episode of 2-hour restraint stress did not alter brain tryptophan 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in water-treated repeatedly restrained rats but decreased tryptophan and increased 5-HT concentration in ethanol-treated rats. Ethanol-treated unrestrained and ethanol-treated repeatedly restrained rats exhibited higher levels of tryptophan 5-HT and 5-HIAA than their respective water-treated controls. Injecting 8-OH-DPAT at a dose of 0.25 mg/kg elicited comparable hyperactivity syndrome in water- and ethanol-treated rats but decreased 5-HT synthesis more in ethanol-treated than in water-treated rats.

Conclusions: The present study shows that ethanol administration for 2 to 3 weeks, although it increases brain 5-HT metabolism, impairs adaptation by increasing the effectiveness of negative feedback control over 5-HT synthesis.