In rats, a hexarelin‑like peptide called EP 80661 makes male rats get erections by raising nitric‑oxide levels in a brain area that controls sexual function. Turning on GABA‑A receptors with muscimol or opioid receptors with morphine blocks both the erection and the nitric‑oxide rise, and these blocks can be undone with specific antagonists. The findings show that GABA and opioid pathways can counteract hexarelin‑induced sexual effects, at least in rats.

The effect of muscimol, a GABA(A) receptor agonist, and of morphine, an opioid receptor agonist, on penile erection induced by the hexarelin analogue peptide EP 80661 (GAB-D-Trp(2-Me)-D-Trp(2-Me)-LysNH(2)) and on the increase in the concentration of NO(2)(-) and NO(3)(-) that occurs concomitantly in the dialysate obtained from the paraventricular nucleus (PVN) of the hypothalamus by intracerebral microdialysis, was studied in male rats. Muscimol (50, 100 and 200 ng) and morphine (0.1, 0.5, 1 and 5 microg) given into the PVN dose-dependently reduced penile erection induced by EP 80661 (1 microg) injected into the PVN. The reduction of penile erection was parallel to a decrease of the concomitant NO(2)(-) and NO(3)(-) increase that occurs in the paraventricular dialysate in these experimental conditions. Muscimol and morphine effects on EP 80661-induced penile erection and NO(2)(-) increase were prevented by the prior administration into the PVN of bicuculline (250 ng) and naloxone (5 microg), respectively. The present results show that the activation of GABA(A) receptors and of opioid receptors in the PVN reduces penile erection induced by hexarelin analogue peptides by reducing the increase in NO activity that occurs in this hypothalamic nucleus in these experimental conditions.