The kisspeptin derivative - kissorphin reduces the acquisition, expression and reinstatement of ethanol-induced conditioned place preference in rats.

Research has shown that opioids are involved in the rewarding effects of ethanol. Neuropeptyde FF (NPFF) has been described as an anti-opioid peptide because it, in many cases, inhibits opioid and ethanol effects in rodents. Kissorphin (KSO) is a new peptide derived from kisspeptin-10 with structural similarities to NPFF. This peptide possesses NPFF-like biological activity in vitro. The aim of the current study was to investigate whether a KSO (Tyr-Asn-Trp-Asn-Ser-Phe-NH2) influences the acquisition, expression and reinstatement of ethanol-induced conditioned place preference (EtOH-CPP) in rats. The EtOH-CPP was established (conditioning for 5 days) by intraperitoneal (i.p.) administration of EtOH (1 g/kg, 20%, w/v) using an unbiased procedure. After that, one group of rats were used in final post-conditioning testing (expression of CPP) and the other group received priming injection of EtOH after 10 days of extinction (reinstatement of CPP). Our experiments showed that KSO, given intravenously (i.v.) at the doses of 1, 3 and 10 nmol before every EtOH administration inhibited the acquisition, and given acutely before the post-conditioning test or before the priming dose of EtOH inhibited the expression and reinstatement of EtOH-CPP, respectively, in a dose-dependent manner. KSO given itself, neither induced place preference nor aversion and did not alter locomotor activity and coordination of rats. These results suggest that KSO can alter rewarding/motivational effects of EtOH. These data suggest this peptide possesses an anti-opioid character.