Comparison of the phenotype of NK1R−/− mice with pharmacological blockade of the substance P (NK 1) receptor in assays for antidepressant and anxiolytic drugs

Abstract:

The phenotype of NK1R−/− mice was compared with that of acute pharmacological blockade of the tachykinin NK 1 receptor on sensorimotor function and in assays relevant to depressive illness and anxiety. The dose range for L-760735 and GR205171 that was associated with functional blockade of central NK 1 receptors in the target species was established by antagonism of the behavioural effects of intracerebroventricular NK 1 agonist challenge in gerbils, mice and rats. The caudal grooming and scratching response to GR73632 was absent in NK1R−/− mice, confirming that the receptor had been genetically ablated. There was no evidence of sedation or motor impairment in NK1R−/− mice or following administration of L-760735 to gerbils, even at doses in excess of those required for central NK 1 receptor occupancy. In the resident–intruder and forced swim test, the behaviour of NK1R−/− mice, or animals …

Año de publicación:

2001

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Fuente:

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