Central effects of urotensin-II following ICV administration in rats

Urotensin-II (U-II) has recently been identified as an agonist for the G-protein-coupled receptor, GPR14. Detection of both U-II and GPR14 mRNA in the brain and spinal cord is consistent with a role for U-II in the CNS. However, the effects of central administration of U-II in rodents have not been reported previously.

To determine the localisation of GPR14 mRNA in rat tissues and to investigate the behavioural and endocrine effects of human U-II (hU-II) following intracerebroventricular (ICV) administration in rats.

Experiments were carried out in male Sprague-Dawley rats. Expression of GPR14 mRNA in rat brain was determined by semi-quantitative RT-PCR. Effects of hU-II on general behaviours were assessed by an observer and the motor activity response was measured by an automated activity monitor. Plasma hormones and [DOPAC + HVA]/[DA] and [5-HIAA]/[5-HT] ratios in five brain areas were measured 20 min post-hU-II (ICV).

GPR14 mRNA expression was found in whole brain tissue and in all CNS regions tested. GPR14 mRNA expression was also detected in the periphery; highest levels were found in the heart. Following ICV administration, hU-II (3-10 micrograms ICV) increased rearing and grooming, and increased motor activity in a familiar environment. Further, hU-II increased plasma prolactin and TSH but did not affect levels of corticosterone. hU-II had no effects on dopamine or 5-HT levels or their metabolites in the frontal cortex, hippocampus, hypothalamus, striatum and nucleus accumbens.

These data provide further insight into the distribution of GPR14 mRNA within the CNS and show for the first time that hU-II causes marked behavioural and endocrine effects.