Ethanol increases γ-aminobutyric acid release in the tuberomammillary nucleus but not in the prefrontal cortex in rats.

BACKGROUND

γ-Aminobutyric acid (GABA) is essential for the central sedative/hypnotic actions of ethanol. The tuberomammillary nucleus (TMN), the exclusive source of forebrain histaminergic innervation, functions as the principal arousal controller. Nevertheless, direct demonstration that ethanol modulates GABA release within the TMN remains elusive.

METHODS

In-vivo microdialysis was used to harvest dialysate from the prefrontal cortex (PFC) and TMN of anesthetized rats after systemic ethanol administration. GABA levels in the dialysate were quantified by HPLC with fluorometric detection.

RESULTS

Within the dose range of 1.5-2.5 g/kg, ethanol (intraperitoneally) did not significantly affect GABA release in the PFC during the 4-h postinjection period (P > 0.05). In contrast, the TMN exhibited a rapid, dose-dependent, and sustained increase in GABA release. The peak GABA release reached 139, 147, and 165% of the baseline level following treatment with 1.5, 2.0, and 2.5 g/kg ethanol, respectively, with the increase persisting until the end of the 4-h observation period at the 2.5 g/kg dose. During the first 2 h after injection, the total amounts of GABA released in the TMN for the three doses of ethanol were 1.16 ± 0.11, 1.94 ± 0.27, and 3.73 ± 0.46 pmol, which were significantly greater than those in the saline control group (0.69 ± 0.08 pmol, P < 0.05 or P < 0.01).

CONCLUSION

Ethanol selectively augments GABAergic output in the TMN while leaving the PFC release unchanged, indicating that the sedative/hypnotic action of ethanol is mediated, at least partially, by enhanced GABA release confined to the TMN.