5-HT1 and 5-HT2 receptor agonists blunt (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-stimulated GH secretion in prepubertal male rats

Objective: Excitatory amino acids, gamma -amino butyric acid (GABA), seroto nin and catecholamines are involved in the control of GH secretion. The act ions of these neurotransmitters are interconnected, and recently we showed that the stimulatory effect of GABA was blocked by MK-801, an antagonist of N-methyl-D-aspartate receptors. The present experiments were carried out t o analyze the interrelationships between (+/-)-alpha -amino-3-hydroxy-5-met hylisoxazole-4-propionic acid (AMPA) receptors and serotoninergic and catec holaminergic pathways in the control of GH secretion in prepubertal (16-23- day-old) male rats. Design and Methods: The GH response to AMPA was analyzed in animals pretrea ted with 5-hydroxytryptophan methyl ester (5-HTP) plus fluoxetine (a precur sor of 5-hydroxytryptamine (5-HT) synthesis and a blocker of 5-HT re-uptake ), R (+)-8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT, an agonist of the 5-HT1 receptors), (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochlori de (DOI) and alpha -methyl-5-hydroxytryptamine (agonists of 5-HT2 receptors ), I-phenylbiguanide (an agonist of 5-HT3 receptors), or alpha -methyl-p-ty rosine (alpha -MPT) and diethyldithiocarbamate (DDC) (blockers of catechola mine synthesis). Results: Basal GH secretion remained unchanged in prepubertal rats after ac tivation of the serotoninergic system or blockade of catecholamine synthesi s. The stimulatory effect of AMPA on GH secretion was blocked after activat ion of the serotoninergic system, through specific 5-HT1 and 5-HT2 receptor agonists, In contrast, activation of 5-HT3 receptors potentiated AMPA-stim ulated GH secretion. Conclusions: Serotoninergic receptors modulate the stimulatory effect of AM PA on GH secretion in prepubertal male rats.