GABAA receptors and the hypothalamic-pituitary-gonadal axis: The effects of acute and chronic intermittent ethanol exposure on multiple systems

Ethanol is known to affect GABAA receptors as well as each level of the Hypothalamic-Pituitary-Gonadal (HPG) Axis. GABAA receptors are the major inhibitory receptors in the mammalian central nervous system, and the pharmacological effects of certain drugs have been shown to be dependent upon specific GABAA receptors subunits. Because benzodiazepines and ethanol have similar effect signatures, it has been hypothesized that these drugs share the gamma2-containing GABAA receptors as a mechanism of action. To probe the involvement of the gamma2 subunit in ethanol's actions, spatial memory for the Morris water maze task was tested in gamma2 heterozygous knockout mice and wild type littermate controls following acute ethanol administration at the following doses: 0.0, 1.25, 1.75, and 2.25 g/kg. While baseline learning and memory were unaffected by reduction of gamma2 containing GABAA receptors, ethanol dose-dependently impaired spatial memory equally in gamma2 heterozygous knockouts and wild type littermate controls. The HPG Axis is the endocrine system involved in male reproduction, and those studies examining the effects of chronic ethanol exposure on endocrine functioning have reported testicular atrophy in both adolescent and adult males. Ethanol-induced testicular atrophy has been shown to normalize following the cessation of alcohol exposure, suggesting that chronic ethanol, in adolescents, delays the onset of sexual maturation. To further understand this effect, adolescent, male Sprague-Dawley rats were exposed to chronic ethanol via repeated, acute injections of ethanol at a 5.0 g/kg dose. Chronic ethanol resulted in significantly lowered estimated testicular volumes compared to pair-fed and free-feed controls. A subsequent period of abstinence resulted in a normalizing of chronic ethanol-induced inhibition of estimated testicular volumes.