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dc.contributor.authorNunes-de-Souza, R. L.
dc.contributor.authorCanto-de-Souza, A.
dc.contributor.authorda-Costa, M.
dc.contributor.authorFornari, R. V.
dc.contributor.authorGraeff, F. G.
dc.contributor.authorPela, I. R.
dc.identifier.citationPsychopharmacology. New York: Springer, v. 150, n. 3, p. 300-310, 2000.
dc.description.abstractRationale: Mice exhibit antinociception after a single experience in the elevated plus maze (EPM), an animal model of anxiety. Objective: This study investigated the mechanisms involved in this form of anxiety-induced antinociception. Methods: Nociception was evaluated by means of the writhing test in mice confined either to the open or enclosed arms of the EPM. The effects of systemic (naloxone, midazolam and 8-OH-DPAT) or intra-amygdala (8-OH-DPAT. NAN-190 and midazolam) drug infusions were investigated in mice previously treated i.p. with 0.6% acetic acid, an algic stimulus that induces abdominal contortions. The effects of these drugs on conventional measures of anxiety (% entries and % time in open arms) in a standard EPM test were also independently investigated. Results: Open-arm confinement resulted in a high-magnitude antinociception (minimum 85%, maximum 450%) compared with enclosed arm confinement. The opiate antagonist naloxone (1 mg/kg and 10 mg/kg) neither blocked this open arm-induced antinociception (OAIA) nor modified indices of anxiety in EPM. Administration of midazolam (0.5-2 mg/kg, s.c.) increased OAIA and produced antinociception in enclosed confined animals, as well as attenuating anxiety in the EPM. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.05-1 mg/kg, s.c.) had biphasic effects on OAIA, antagonising the response at the lowest dose and intensifying it at the highest dose. In addition, low doses of this agent reduced anxiety in the EPM. Although bilateral injections of 8-OH-DPAT (5.6 nmol/0.4 mu l) or NAN-190 (5.6 nmol and 10 nmol/0.4 mu l) into the amygdala did not alter OAIA, increased anxiety was observed in the EPM. In contrast, intra-amygdala administration of midazolam (10 nmol and 30 nmol/0.4 mu l) blocked both OAIA and anxiety. Conclusions: These results with systemic and intracerebral drug infusion suggest that 5-HT(1A) receptors localised in the amygdala are not involved in the pain inhibitory processes that are recruited during aversive situations. However, activation of these receptors does phasically increase anxiety. Although the intrinsic antinociceptive properties of systemically administered midazolam confounded interpretation of its effects on OAIA, intra-amygdala injections of this compound suggest that benzodiazepine receptors in this brain region modulate both the antinociceptive and behavioural (anxiety) responses to the EPM.en
dc.sourceWeb of Science
dc.subjectelevated plus-mazept
dc.subject5-HT(1A) receptorpt
dc.titleAnxiety-induced antinociception in mice: effects of systemic and intra-amygdala administration of 8-OH-DPAT and midazolamen
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.description.affiliationUNESP, Fac Ciências Farmaceut Araraquara, PANT, Farmacol Lab, BR-14801902 Araraquara, SP, Brazil
dc.description.affiliationUniv Fed Sao Carlos, Dept Psicol, BR-13560 Sao Carlos, SP, Brazil
dc.description.affiliationUniv São Paulo, Fac Med Ribeirao Preto, Dept Neurol Psiquit & Psicol Med, Ribeirao Preto, Brazil
dc.description.affiliationUniv São Paulo, Fac Cciencias Farmaceut Ribeirao Preto, Farmacol Lab, Ribeirao Preto, Brazil
dc.description.affiliationUnespUNESP, Fac Ciências Farmaceut Araraquara, PANT, Farmacol Lab, BR-14801902 Araraquara, SP, Brazil
dc.rights.accessRightsAcesso restrito
unesp.campusUniversidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Araraquarapt
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