DOES ANTAGONISM OF GLUTAMATERGIC NEUROTRANSMISSION TO HYPOTHALAMIC NEUROSECRETORY CELLS AFFECT THE SECRETION OF GROWTH HORMONE, TESTOSTERONE AND CORTISOL IN THE MALE RHESUS MONKEY?

Abstract

The glutamate receptor of N-methyl-D-aspartate (NMDA) subtype is involved in virtually all aspects of the normal brain function including learning, memory, movement, - cognition, development, growth, reproduction and intermediary metabolism, whereas ketamine hydrochloride (KH), a widely used anesthetic, antagonizes a variety of NMDA receptor mediated actions of the excitatory neurotransmitters. The present study attempts to examine the effect of KH on basal and stimulated growth hormone (GH), testosterone (T) and cortisol secretion in the adult male rhesus monkey (Macaca mulatta). Five conscious chair-restrained adult male rhesus monkeys received a single intravenous (iv) injection of an agonist of NMDA receptor, N-methyl-D, L-aspartate (NMA) (15 mg/kg BW) via the sample line. Blood samples were collected 60 min before and 90 min after the NMA injection at 10-15 min intervals. NMA was dissolved in normal saline immediately before use and passed through a 0.22 flm filter unit at the time of injection. Seven days later, using identical blood sampling regimen, the same animals were bleed under multiple intramuscular injections of KH (initial dose 5 mg/kg BW, followed by 2.5 mg/kg BW). The plasma levels of GH, T and cortisol were determined by using specific assay systems. A single iv injection of NMA resulted in a remarkable increase in circulating concentrations of GH in both conscious chair-restrained and KH anesthetized monkeys within 20-45 min of the administration of the drug. The NMA-induced GH secretion was significantly (p<0.05) higher in KH anesthetized animals compared to conscious chair-restrained monkeys. The mean basal plasma GH concentrations were significantly (p<0.05) higher in KH anesthetized monkeys than conscious animals. Similarly, the administration of NMA induced a significant (p<0.01) increase in T secretion in conscious chair-restrained as well as KH anesthetized monkeys within 70 min of the injection. The increase in T secretion in response to NMA administration was not significantly (p>0.05) different between conscious chair-restrained and KH anesthetized monkeys. Nevertheless, the mean basal plasma T concentrations were significantly (p<0.05) higher in KH anesthetized monkeys compared to conscious chair restrained animals. A single iv injection of NMA elicited a marked (p<0.02) increase in cortisol concentrations in both conscious chair-restrained and KH anesthetized monkeys within 70 min of the administration of the agonist of the NMDA receptor. The NMA dependent release of cortisol was significantly (p<0.00002) decreased in KH anesthetized monkeys compared to consciou chair-restrained animals. Likewise, the mean basal plasma cortisol secretion was significantly reduced in KH anesthetized animals in comparison with conscious chair-restrained monkeys. In conclusion, we report here that KH stimulates both basal and NMA-stimulated GH secretion, increases basal T secretion without affecting the NMA -dependent T release and decreases both basal and NMA-induced cortisol secretion in the adult male rhesus monkey.