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Psychopharmacology (Berl). 2001 Jun;155(4):426-33.

Central effects of urotensin-II following ICV administration in rats.

Author information

1
Neuroscience Research, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. jane_gartlon-1@sbphrd.com

Abstract

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 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.

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 [DOPAC + 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 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.

CONCLUSIONS:

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.

PMID:
11441433
DOI:
10.1007/s002130100715
[Indexed for MEDLINE]

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