title: Place aversion induced by microinjections of C-fragment of substance P into the dorsal periaqueductal gray of rats is mediated by tachykinin NK1 receptors.
abstract: Neural circuits in the dorsal periaqueductal gray matter (dPAG) play an important role in the integration of defensive behavior. The neurokinin substance P causes conditioned place aversion when administered into this region. The present study examined whether these effects may be mimicked by its carboxy-terminal amino acid sequence and whether they are influenced by prior treatment with the tachykinin NK1 receptor antagonist WIN51,708. The behavioral testing apparatus is a circular open field consisting of 4 uniform quadrants that are equally preferred by the rats prior to drug treatments. For conditioning, rats received drug injections on three consecutive days and were placed into their assigned quadrant. The carboxy-terminal analog (17.5 pmol/0.2 microl) applied into the dPAG produced place aversion effects with reduced time spent in the drug-paired quadrant on the testing day. The effects of the carboxy-terminal analog was antagonized by pretreatment with WIN51,708 (20 mg/kg, i.p.). Microinjection of WIN51,708 (20 mg/kg, i.p.), by its own, did not produce significant effects. These findings suggest that previous reports showing conditioned place aversion effects of SP injected into the dPAG are encoded by its carboxy-terminal sequence and due to its action on tachykinin NK1 receptors.
authors.affiliation: Laboratório de Psicobiologia, FFCLRP, campus USP, av Bandeirantes 3900, 14049-901, Ribeirão Preto, SP, Brazil.
authors.forename: J E
authors.initials: JE
authors.lastname: De Araújo
authors.forename: J P
authors.initials: JP
authors.lastname: Huston
authors.forename: M L
authors.initials: ML
authors.lastname: Brandão
mesh_terms: D000731:Androstanes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections / Q000379:methods; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D013997:Time Factors
chemical_list: D000731:Androstanes; D001562:Benzimidazoles; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; C086111:WIN 51708; D013373:Substance P