Roles of .GAMMA.-aminobutyric acid and serotonin in the arcuate nucleus in the control of prolactin and luteinizing hormone secretion.

Self Cite

The role of GABA neurons in the control of pulsatile release of LHRH was investigated by checking the effect of the GABAa receptor agonist, muscimol, and antagonist, bicuculline, on the electrical activity of the luteinizing hormone-releasing hormone (LHRH) pulse generator in the ovariectomized rat fitted with chronically implanted electrode arrays in the medial basal hypothalamus. In untreated control animals, the hypothalamic multiunit activity (MUA) exhibited, at an average of 20.5-min intervals, characteristic increases (volleys), each of which was associated with the initiation of an LH pulse. A bolus i.v. injection of muscimol (2 mg/kg) significantly increased the interval between MUA volleys and LH pulses without affecting the pulse amplitude. Continuous i.v. infusion of saline increased the interval between MUA volleys to an average of 24.1 min without affecting the LH pulse amplitudes. Bicuculline infusion (10 mg/kg/h) altered neither the interval between MUA volleys nor the pulsatile release of LH. This was further checked in the condition where presynaptic inhibition by opioid peptides on the noradrenergic system was presumably decreased by naloxone. Naloxone infusion (0.5 or 0.7 mg/ kg/h) caused the MUA volleys to occur markedly frequently, an average of 13.8-min intervals. The interval during combined infusion of bicuculline with naloxone was an average of 16.2 min, suggesting that bicuculline could not decrease the interval that was set by naloxone. The results show that, although exogenous GABAa receptor agonist is capable of inhibiting the activity of LHRH pulse generator, the reduction in the endogenous GABAa receptor activity does not cause a significant effect, suggesting a minor role of inhibitory GABA neurons in the control of pulsatile release of LHRH. Further, together with the well-known fact that activation of GABAa receptor hyperpolarizes neurons postsynaptically, it is assumed that the GABAergic system, unlike the opioidergic one, is not involved in the presynaptic inhibition of the adrenergic receptor system which is probably implicated in the frequency control of LHRH pulse generator.

Section: Discussionsupporting

confidence: 89%

Effects of Gamma-Aminobutyric Acid-A Receptor Antagonist Bicuculline, on the Electrical Activity of Luteinizing Hormone-Releasing Hormone Pulse Generator in the Ovariectomized Rat

Kimura

Sano²,

Hiruma³

et al. 1993

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“…This suggests that the GABAergic inhibition of pul satile LH secretion [1,2] is partially mediated by GABAb receptors, in addition to a mediation by classic GABAa receptors [4,5], although the relative contribution of these receptors is unknown at present. The GABAb re ceptor-mediated suppression of the LH pulse frequency may have a causal relationship to the baclofen-induced inhibition of the preovulatory LH surge [8,10], as dis cussed elsewhere [8].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that y-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the central nervous system, is involved in the neuroendocrine control of the episodic LH secretion. The existing pulsatile LH secre tion is inhibited by reducing the degradation of the en dogenous GABA [1] or by centrally applying GABA in ovariectomized rats [2]. LH pulses are preceded by a significant reduction of preoptic/anterior hypothalamic GABA release [3], Receptors mediating the GABAergic transmission have been classified into two major subtypes, GABAa and GABAb, according to their pharmacological proper ties.…”

mentioning

confidence: 99%

Modulation of Pulsatile LH Secretion by Baclofen, a Selective GABA<sub>B</sub> Receptor Agonist, in Ovariectomized Rats

Akema

Kimura

1992

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The effect of activation of central γ-aminobutyric acid β (GABAB) receptors on pulsatile luteinizing hormone (LH) secretion was examined in unanesthetized ovariectomized rats. Intraventricular injections of 2 or 10 µg baclofen, a selective GABAB receptor agonist, usually arrested the existing pulsatile LH secretion for a short period, then LH pulses resumed with reduced frequencies and increased amplitudes. The increase in the pulse amplitude was not necessarily accompanied by a reduction in the pulse frequency, but was observed even after nonelongated interpulse intervals in animals receiving the GABA agonist. Mean LH levels showed complex bi- and triphasic fluctuations after the central administration of high and low doses of baclofen, respectively. It was concluded that central GABAB receptors are involved in the modulatory mechanism affecting the LH pulse frequency and amplitude in the ovariectomized rat.

“…This amino acid also affects several as pects of neuroendocrine function by actions in the brain, in cluding in the ARC [22]. In fact, implantation of GABA directly into the ARC has been reported to decrease the release of lu teinizing hormone [23]. Again, extracellular recordings have in dicated that GABA decreases the activity of most ARC neurons [24], GABA acts on at least two different receptors.…”

mentioning

confidence: 99%

Neurons in the Rat Arcuate Nucleus Are Hyperpolarized by GABA<sub>B</sub> and μ-Opioid Receptor Agonists: Evidence for Convergence at a Ligand-Gated Potassium Conductance

Loose

Rønnekleiv

Kelly³

1991

Both γ-aminobutyric acid (GABA) and the endogenous opioid peptides have pervasive effects on neuroendocrine function. This study examined the effects of selective activation of GABAB and/or µ-opioid receptors on neurons of the arcuate nucelus (ARC) of the rat hypothalamus using intracellular recording of cells in a hypothalamic slice. Some recorded neurons were filled with biocytin allowing subsequent identification and immunocytochemical evaluation for the presence of β-endorphin. ARC neurons exhibited a broad array of active and passive conductances. Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGOL), a µ-opioid receptor agonist, inhibited spontaneous firing, hyperpolarized 68% of ARC cells in a dose-dependent manner and increased cell conductance. Baclofen, a GABAB receptor agonist, hyperpolarized all cells tested. The reversal potentials for both the DAGOL- and baclofen-induced currents were near that of a potassium conductance. Maximal activation by either of the agonists blocked the effects of the other agonist. Identified β-endorphin cells were inhibited by both DAGOL and baclofen. The results of these in vitro studies suggest that GABAB and µ-opioid receptors are coupled to the same set of potassium channels and that these channels directly and powerfully inhibit most ARC cells, including β-endorphin neurons. We propose that convergence of inhibitory influences at the ligand-gated potassium conductance described here may be an important site of interaction for opioidergic, GABAergic and other putative neurotransmitter systems in the control of neuroendocrine circuits by the ARC.