Hyperresponsiveness to the Inhibitory Action of Dopamine Agonists on Luteinizing Hormone Secretion in the Monosodium-L-Glutamate-Treated, Orchidectomized Rat

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Abstract
The tuberoinfundibular (A12) dopaminergic pathway, which originates in the arcuate and periventricular nuclei, is thought to play an inhibitory role in the regulation of episodic luteinizing hormone (LH) secretion. Neonatal treatment of rats with the neurotoxin monosodium-L-glutamate (MSG) causes extensive damage to the arcuate nuclei and up to 60% depletion of dopamine (DA) in the mediobasal hypothalamus. We hypothesized that such DA depletion should result in a hyperresponsiveness to subsequent administration of a DA agonist. To test this hypothesis, male rats were treated neonatally with MSG. Control rats received injections of equiosmotic saline. As adults the rats were orchidectomized and fitted with indwelling venous catheters. Blood samples were taken from these unanesthetized, unrestrained rats at 5-min intervals for a 1-hour period, at which time the animals received an intraperitoneal injection of one of the following drugs: apomorphine (0.8 mg/kg, a DA receptor agonist), bromocriptine (8.0 mg/kg, a DA receptor agonist), 0.9% saline (vehicle for apomorphine) or 95% ethanol (vehicle for bromocriptine). Blood sampling was continued for a further 2–2.5 h. Plasma LH was measured by RIA. Both apomorphine and bromocriptine produced striking inhibition of circulating LH levels in MSG-treated rats. Neither of the control treatments altered pulsatile LH secretion patterns. Administration of exogenous gonadotropin-releasing hormone produced LH peaks in all animals so treated, including those whose endogenous LH secretion had been inhibited by the DA agonists. These findings suggest that the depletion of DA induced by neonatal MSG treatment results in a supersensitivity to DA agonists. Furthermore, they support the theory that tuberoinfundibular DA is an inhibitory regulator of episodic LH secretion in the castrate rat, and that this inhibitory effect occurs at a suprapituitary site.