The behavioural effects of a novel substance P analogue following infusion into the ventral tegmental area or substantia nigra of rat brain.
The behavioural response following infusion of a novel, stable substance P (SP) analogue, DiMe-C7, into the ventral tegmental area (VTA) of rats was characterized and contrasted with the response to an equal dose of the parent compound SP. DiMe-C7 produced a longer-lasting behavioural stimulation than SP as evidenced in several behaviours, including locomotor activity, wet dog shakes, rearing and grooming. DiMe-C7-induced locomotor activity and rearing were potentiated by concurrent peripheral administration of D-amphetamine and blocked by pretreatment with haloperidol. Such responses to DiMe-C7 may thus be dependent upon dopaminergic activity. When given immediately following VTA infusion of DiMe-C7, morphine decreased, while naloxone had no effect upon most behavioural measures. The effect of methysergide on DiMe-C7 or SP into the substantia nigra reticulata produced a pattern of responses similar to nature to those produced by VTA infusion but different with respect to time course. These findings suggest that DiMe-C7 is a metabolically stable analogue of substance P which manifests prolonged actions on behaviour when centrally administered. Further, a role for central dopaminergic mechanisms is implicated in DiMe-C7-induced behavioural action.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010446:Peptide Fragments; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects*; D013681:Tegmentum Mesencephali / Q000187:drug effects*
D010446:Peptide Fragments; D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D011985:Receptors, Serotonin; D013373:Substance P; C032720:substance P (5-11), pGlu(5)-MePhe(8)-MeGly(9)-; D011761:Pyrrolidonecarboxylic Acid