Reinforcing effects of neurokinin substance P in the ventral pallidum: mediation by the tachykinin NK1 receptor.
The neurokinin substance P has reinforcing effects when administered into the nucleus basalis of the rat's ventral pallidum and these effects are encoded by its carboxy-terminal amino acid sequence. The present study examined the effect of prior treatment with the tachykinin NK1 receptor antagonist WIN51,708 on the conditioned place preference produced by intrabasalis injection of substance P and its carboxy-terminal heptapeptide analog dimethyl-C7. Pretreatment with WIN51,708 (10 and 20 mg/kg, i.p.) dose-dependently reversed the place preference produced by intrabasalis substance P (0.74 pmol). The carboxy-terminal analog dimethyl-C7 (0.74 pmol) was also found to act as a reinforcer following injection into the nucleus basalis region, but unlike for substance P, the behavioral effects of dimethyl-C7 could not be completely antagonized by joint administration of the NK1 antagonist. When injected alone, WIN51,708 did not influence the preference behavior. These findings suggest that the reinforcing effects of substance P in the nucleus basalis region might be mediated via NK receptive sites. The failure of WIN51,708 to completely antagonize the behavioral effects of dimethyl-C7 is interesting in the light of evidence, indicating that the carboxy-terminal substance P analog shows higher affinity for the tachykinin NK3 than for the NK1 receptor subtype.
D000731:Androstanes / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology