Central effects of urotensin-II following ICV administration in rats

Rationale: Urotensin-II (U-II) has recently been identified as an agonist for the G-protein-coupled receptor, GPR14. Detection of both U-II and GPR 14 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. Objectives: 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. Methods: 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 [DDPAC+HVA]/[DA] and [5-HIAA]/[5-HT] ratios in five brain areas were measured 20 min post-hU-II (ICV). Results: 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 mug 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. Conclusions: GPR14 mRNA within the CNS and show for the first time that hU-II causes marked behavioural and endocrine effects.