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 behavioral effects elicited by intracerebroventricular (i.c.v.) substance P (SP) and neurokinin A (NKA) injections were examined in conscious, freely moving rats. The cardiovascular responses to equimolar doses of both peptides were identical, however, the pattern of the behavioral responses differed. Relative to SP, NKA was weaker in eliciting hindquarter grooming but more effective in eliciting wet dog shakes. SP pretreatment (50 pmol) desensitized the cardiovascular and behavioral responses to both, subsequent injections of SP (50 pmol) as well as of NKA (50 or 500 pmol) injected 30 or 60 min after SP, indicating cross-desensitization. NKA pretreatment (50 pmol) partly reduced the cardiovascular but not the behavioral responses to subsequent equimolar doses of 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 of NKA (500 pmol). Of all behavioral manifestations to i.c.v. SP, only hindquarter grooming was attenuated by pretreatment with either dose of NKA. The equal potency of SP and NKA in eliciting the cardiovascular effects but different pattern of behavioral responses to these peptides suggest an involvement of different types of tachykinin receptors in mediating the central effects of the two peptides. The fact that NKA induced cross-desensitization selectively to one type of behavioral manifestations elicited by SP, indicates the existence of two subtypes of SP (NK1) receptors in the rat brain.