The tachykinin NK 3 receptor agonist senktide induces locomotor activity in male Mongolian gerbils

• Published in: European journal of pharmacology Vol. 600; no. 1; pp. 87 - 92
• Main Authors: Nordquist, Rebecca E., Durkin, Sean, Jacquet, Aurélie, Spooren, Will
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2008
• Subjects: Antipsychotic; Aprepitant; Gerbil; Locomotor activity; MK869; Neurokinin; Osanetant; SB222200; SB223412; Senktide; SR142801; Tachykinin; Talnetant; Aprepitant; Senktide; Talnetant; SB222200; Neurokinin; SB223412; Antipsychotic; Osanetant; SR142801; Gerbil; Tachykinin; MK869; Locomotor activity
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.10.011

The tachykinin family of receptors has been of strong interest recently due to the potential of the tachykinin NK 3 receptor antagonism in treatment of schizophrenia. However, critical differences in the tachykinin NK 3 receptor between rats, mice and humans make rats and mice less acceptable species for testing tachykinin NK 3 receptor antagonism. This has led to testing of tachykinin NK 3 receptor activity in gerbils and guinea pigs. As these species are much less common laboratory animals than rats and mice, there is a relative paucity of in vivo testing models for tachykinin NK 3 receptor activation. In the present study, locomotor activity induced by the tachykinin NK 3 receptor agonist senktide was characterized. Injection of senktide i.c.v. was found to dose-dependently induce hyperlocomotion from a dose of 0.06 nmol to the maximal dose tested, 0.6 nmol. Locomotion induced by 0.1 nmol of senktide could be blocked by injection of the tachykinin NK 3 receptor antagonists SB222200 (10 and 30 mg/kg i.p.) and talnetant (SB223412; 10 and 30 mg/kg i.p.), as well as by osanetant (SR142801; 10 and 30 mg/kg i.p.) when administered in a vehicle containing vitamin E and glycofurol. Senktide-induced activity was also reversed by the antipsychotics haloperidol (0.3 and 1 mg/kg p.o.) and risperidone (1 mg/kg p.o.), but not by the serotonin 5HT 2a/c receptor antagonist MDL100907 (tested at 0.1, 0.3 and 1 mg/kg p.o.). Hyperlocomotion induced by 0.03 nmol of senktide was potentiated by antagonism of the tachykinin NK 1 receptor with aprepitant (1, 3 and 10 mg/kg, p.o.). Thus, hyperlocomotion induced by senktide in gerbils is a tachykinin NK 3 receptor-mediated behavior that is appropriate for use in testing tachykinin NK 3 receptor activity of novel compounds.