Role of kisspeptin/GPR54 pathway in mediating morphine's effects on hypothalamic NPY gene expression in male rats

Intra-hypothalamic neural pathways including neuropeptide Y (NPY), opioids and kisspeptin are among the most important regulators of reproductive function. Morphine decreases NPY and kisspeptin (Kiss1) gene expression, while kisspeptin or naloxone increases NPY gene expressions. In the present study the role of kisspeptin/GPR54 pathway was investigated in mediating morphine's effects on hypothalamic NPY gene expression in male rats.

Forty five male Wistar rats weighing 230-250 g in 9 groups (in each group n = 5) received saline, morphine (5 mg/kg), naloxone (2 mg/kg), kisspeptin (1nM), peptide 234 (1 nM) or co-injection of naloxone/morphine, kisspeptin/morphine, kisspeptin/naloxone, and morphine/peptide234. Naloxone and morphine were injected subcutaneously, while kisspeptin and peptide 234 were injected into third cerebral ventricle.  The hypothalamus of the animals was removed and relative NPY mRNA levels measured by RT-PCR.

Morphine significantly decreased NPY gene expression, while kisspeptin significantly increased the expression. NPY gene expression was significantly increased by kisspeptin/morphine compared to saline. However, the expression was significantly decreased by kisspeptin/morphine compared to kisspeptin alone. The injection of kisspeptin/naloxone increased NPY gene expression compared to saline, naloxone or kisspeptin alone. This increase was statistically significant compared to saline or naloxone groups. Morphine/peptide234 decreased NPY gene expression compared to saline or morphine but the decrease was only statistically significant compared to saline.

It seems that in addition kisspeptin/GPR54 pathway, other intra-hypothalamic neural pathways are also involved in the inhibitory effects of morphine on NPY neurons activity.