Use of selective antagonists to dissociate the central cardiovascular and behavioural effects of tachykinins on NK1 and NK2 receptors in the rat.

Abstract

1. The effects of intracerebroventricular (i.c.v.) pretreatment with selective NK1 ((+/-)-CP 96,345), NK2a (MEN 10,207; MEN 10,376) and NK2b (R 396) tachykinin receptor antagonists on the cardiovascular and behavioural responses to i.c.v. substance P (SP) and neurokinin A (NKA) were studied in conscious rats. 2. SP and NKA (25 pmol) induced mean arterial blood pressure and heart rate increases of the same magnitude and duration. The cardiovascular responses to both peptides were accompanied by excessive face washing, sniffing, grooming and wet dog shakes. 3. The cardiovascular responses to SP but not to NKA were attenuated by pretreatment with a NK1 receptor antagonist, (+/-)-CP 96,345. Of the behavioural responses, only face washing was significantly inhibited. 4. The cardiovascular and behavioural effects of NKA but not of SP were significantly attenuated by pretreatment with the selective NK2b receptor antagonist, R 396. 5. The selective NK2a receptor antagonists, MEN 10,207 and MEN 10,376, did not affect the cardiovascular and behavioural responses to either SP or NKA. 6. These results suggest, firstly, that the cardiovascular and behavioural effects of i.c.v. SP are mediated by NK1 receptors; secondly, that NKA injected i.c.v. does not interact with NK1 receptors but with another type of tachykinin receptor which may belong to the NK2b subclass. These findings provide pharmacological evidence for the existence of functionally active NK2 receptors in the rat brain.