SUBSTANCE-P AND NEUROKININ-A INDUCED DESENSITIZATION TO CARDIOVASCULAR AND BEHAVIORAL-EFFECTS - EVIDENCE FOR THE INVOLVEMENT OF DIFFERENT TACHYKININ RECEPTORS

Desensitization and cross-desensitization to the cardiovascular and be havioral effects elicited by intracerebroventricular (i.c.v.) substanc e P (SP) and neurokinin A (NKA) injections were examined in conscious, freely moving rats. The cardiovascular responses to equimolar doses o f both peptides were identical, however, the pattern of the behavioral responses differed. Relative to SP, NKA was weaker in eliciting hindq uarter grooming but more effective in eliciting wet dog shakes. SP pre treatment (50 pmol) desensitized the cardiovascular and behavioral res ponses to both, subsequent injections of SP (50 pmol) as well as of NK A (50 or 500 pmol) injected 30 or 60 min after SP, indicating cross-de sensitization. NKA pretreatment (50 pmol) partly reduced the cardiovas cular but not the behavioral responses to subsequent equimolar doses o f NKA. The cardiovascular responses to SP (50 pmol) were reduced only 30 min but not 60 min after pretreatment with a 10 times higher dose o f NKA (500 pmol). Of all behavioral manifestations to i.c.v. SP, only hindquarter grooming was attenuated by pretreatment with either dose o f NKA. The equal potency of SP and NKA in eliciting the cardiovascular effects but different pattern of behavioral responses to these peptid es suggest an involvement of different types of tachykinin receptors i n mediating the central effects of the two peptides. The fact that NKA induced cross-desensitization selectively to one type of behavioral m anifestations elicited by SP, indicates the existence of two subtypes of SP (NK1) receptors in the rat brain.