Localization of Fos-like immunoreactivity induced by the NK3 tachykinin receptor agonist, senktide, in the guinea-pig brain.

1. The effects of intracerebroventricular (i.c.v.) administration of the NK3 tachykinin receptor agonist, senktide (10 nmol each side), in guinea-pigs pretreated with the selective NK3 tachykinin receptor antagonist, SR142801 (3 mg kg(-1) subcutaneous, s.c., 30 min before senktide), or its less active enantiomer, SR142806 (3 mg kg(-1) s.c. 30 min before senktide), on behaviour and on the distribution of Fos-like immunoreactivity (Fos-LI) in central neurones were investigated. Guinea-pigs were chosen for the study since they possess NK3 tachykinin receptors with pharmacological characteristics similar to those in man. 2. Wet-dog shakes, but not locomotor activity, elicited by senktide i.c.v. were significantly reduced by SR142801 but not by SR142806, confirming the involvement of NK3 tachykinin receptors in wet-dog shake behaviour. 3. Senktide induced increased numbers of Fos-LI neurones in the following brain areas: frontal, parietal and piriform cortex, the lateral septum, the CA1, CA2, subiculum and dentate gyrus of the hippocampus, most areas in the amygdala, thalamus and hypothalamus, medial geniculate nucleus and the ventral cochlear nucleus. Pretreatment with SR142801, but not with SR142806, before administration of senktide inhibited Fos-LI expression in the cingulate cortex, dentate gyrus of the hippocampus, some regions of the thalamus, hypothalamus and amygdala and the ventral cochlear nucleus. 4. The present results are the first demonstration that senktide induces Fos-LI in widespread areas of the guinea-pig brain. It is proposed that NK3 tachykinin receptors may play a more extensive role in the control of diverse brain functions, including cortical processing, learning and memory, neuroendocrine and behavioural regulation, than is currently recognized.