A gamma-aminobutyric acid(B) agonist reverses the negative feedback effectof testosterone an gonadotropin-releasing hormone and luteinizing hormone secretion in the male sheep

Infusion of baclofen, a GABA(B) agonist, into the medial basal hypothalamus (MBH) of castrated rams rapidly increases LH pulse amplitude without alter ing pulse frequency. The objectives of this study were to determine whether baclofen infusion increased LH in testosterone (T)-treated and intact rams , the increased LH was due to increased GnRH release, and FSH secretion als o was increased. In the first experiment we tested the main effects and int eraction of baclofen and T on FSH and LH pulse patterns in castrated rams ( n = 7). In the second experiment we determined whether baclofen affected Gn RH and LH pulses in intact males. Microdialysis guide cannulae were implant ed bilaterally into the MBH. After recovery of the animal from surgery, the MBH was perfused using concentric microdialysis probes (2-mm tip) with art ificial cerebrospinal fluid (aCSF) for a 3-h control period followed by eit her aCSF or 1 mM baclofen for 4 h. Blood samples were taken at 10-min inter vals. T suppressed mean LH concentrations (10.4 +/- 1.3 vs. 3.3 +/- 1.3 ng/ ml) such that LH pulses were undetectable in some T-treated animals during the control period. The change (control period vs. drug infusion period) in mean LH was greater in response to baclofen than in response to aCSF and w as not altered by T. The baclofen X T interaction was nonsignificant. Mean FSH was decreased by T, but was not altered by baclofen. In the second expe riment hypophyseal portal blood was collected coincident with microdialysis . infusion of baclofen into the MBH of intact males (n = 7) resulted within 1 h in the onset of frequent and robust GnRH pulses (0.10/h before baclofe n vs. 1.57/h after baclofen) that were followed either immediately or gradu ally by coincident LII pulses. One interpretation is that baclofen acts dow nstream of the site of action of T. GABA(B) receptors may regulate pulse am plitude in both the presence and absence of T and regulate pulse frequency by modulating the inhibitory effect of T.