Regional Variation in γ‐Aminobutyric Acid Turnover: Effect of Castration on γ‐Aminobutyric Acid Turnover in Microdissected Brain Regions of the Male Rat

Abstract

This study compared the turnover of GABA neurons in different brain areas of the male rat and examined the effect of castration on GABA turnover in regions of the brain associated with the control of gonadotropin secretion. To estimate GABA turnover, GABA was quantified by HPLC in microdissected brain regions 0, 30, 60, 90, and 120 min after inhibition of GABA degradation by aminooxyacetic acid (100 mg/kg, i.p.). GABA accumulation was linear in all areas for 90 min (p < 0.01), and GABA turnover was estimated as the slope of the line formed by increased GABA concentration versus time, determined by linear regression. There was considerable regional variation both in the initial steady-state concentrations of GABA and in the rates of GABA turnover. Of 10 discrete brain structures, GABA turnover was highest in the medial preoptic nucleus and lowest in the caudate nucleus. Turnover times in the terminal fields of known GABAergic projection neurons ranged sevenfold, from 2.6 h in the substantia nigra to 0.4 h in the lateral vestibular nucleus. The effect of castration on GABA turnover in 13 microdissected brain regions was investigated by measuring regional GABA concentrations before and 30 min after injection of aminooxyacetic acid in intact rats or 2 or 6 days postcastration. Following castration, steady-state GABA concentrations were increased, and GABA turnover decreased in the diagonal band of Broca, the medial preoptic area, and the median eminence. GABA turnover increased in the medial septal nucleus and was unaffected in the cortex, striatum, and hindbrain. These results are consistent with the hypothesis that testosterone negative-feedback control of luteinizing hormone-releasing hormone involves steroid-sensitive GABAergic neurons in the rostral and medial basal hypothalamus.

GABAergic Regulation of Lordosis: Influence of Gonadal Hormones on Turnover of GABA and Interaction of GABA with 5-HT

“…Turnover rates are relative, but are valid indicators of activity when assumptions of the technique are satisfied and appropriate between-group comparisons are made [14]. Previous studies show that accumulation rates in preoptic-hypothalamic nuclei at this dose are selective and linear up to 1 h post-AOAA [5, 14]. …”

“…GABA was measured as previously described [5, 6, 11]using high-performance liquid chromatography (HPLC) with electrochemical detection following precolumn derivatization of the sample with o -phthalaldehyde (OPA) and β-mercaptoethanol (BME). A Waters Associates 590 pump and WISP 717 automated sample injector with refrigeration, which maintained samples at 4°C, was used.…”

“…These nuclei, VMN, mPOA and MCG, provide the critical sites and interconnections, which activate the hormone-dependent reflex. Moreover, gonadal hormones appear to regulate levels of GABA [4, 5, 6, 7, 8, 9, 10, 11]and its receptor [12]in some of these areas. Taken together, these results suggest that GABA may be critical in mediating hormone-dependent lordosis.…”

“…Previous studies have investigated gonadal hormone effects on GABA activity and shown changes in preoptic-hypothalamic nuclei, but these effects were obtained in studies on hormonal regulation of gonadotropin secretion, not sexual behavior [5, 6, 7, 8, 9, 10]. They show that GABA containing neurons in the preoptic-diagonal band area exert an inhibitory influence on LH release, and that, on the afternoon of proestrus, decreased activity of GABAergic neurons contribute to induction of LH surge [5, 6, 7, 8, 9, 10]. In this study, we measured levels of GABA and its turnover/activity in brain areas, which regulate lordosis after hormone treatments, which induce lordosis, in order to determine whether changes in GABA might also contribute to induction of lordosis.…”

Androgen Receptors in the Posterior Bed Nucleus of the Stria Terminalis Increase Neuropeptide Expression and the Stress-Induced Activation of the Paraventricular Nucleus of the Hypothalamus

“…Further, GABA synthesis and turnover in the brain is remarkably sensitive to alterations in circulating testosterone concentrations (Grattan and Selmanoff, 1993). Thus, we anticipated a local influence for androgen receptors to regulate GAD expression in the posterior BST.…”