Distribution of Fos-like immunoreactivity in guinea-pig brain following administration of the neurokinin-1 receptor agonist, [Sar9,Met(O2)11]substance P
Section snippets
Animal preparation
Adult tricolour guinea-pigs of either sex (from the Central Animal Facility, University of Newcastle) weighing 450–550 g were used. The guinea-pigs were housed in a room maintained at constant temperature (23°C) and on a 12-h/12-h light/dark cycle. Food (standard guinea-pig pellets) and water were available ad libitum, and vitamin C was added to the drinking water daily. Implantation of i.c.v. cannulae was carried out as described previously.14 Guinea-pigs were weighed and anaesthetized with
Effect of [Sar9,Met(O2)11]substance P on locomotor activity and behaviours
Locomotor activity was significantly increased in animals given [Sar9,Met(O2)11]SP (1 nmol each side, i.c.v.) compared with control animals (Fig. 1). The increase in locomotor activity reached significance at 30 min (0.05>P>0.01) and was sustained for the remainder of the 90-min period of observation. Administration of the NK1 receptor antagonist SR 140333 (total dose 12 μg, i.c.v.), but not its less active enantiomer SR 140603, significantly reduced the increase in locomotor activity at 40 min
Discussion
Administration of [Sar9,Met(O2)11]SP produced increased locomotor activity which was inhibited by SR 140333, confirming that this response to [Sar9,Met(O2)11]SP was mediated by NK1 receptors. [Sar9,Met(O2)11]SP produced a wide range of behavioural responses, including circling, turning, cage biting, face washing, grooming, wet-dog shakes, scratching, chewing and vocalization. The most marked increases occurred in circling, face washing and wet-dog shake behaviours, each of which were
Conclusion
The data obtained in the present study have added a functional domain to previous NK1 receptor localization studies by describing the extensive regions of the CNS that may be activated by stimulation of these receptors, and the potential of NK1 receptor antagonists to inhibit activation of these regions.
Acknowledgments
We wish to thank Dr Emonds-Alt of Sanofi Recherche, France, for generous donations of SR 140333 and SR 140603. The work was supported by a project grant to L.A.C. (970799) from the National Health and Medical Research Council of Australia.
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