title: Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze.
abstract: BACKGROUND
  Although 5-HT2 receptors seem to play an important role in anxiety, results from numerous studies are still highly variable. Moreover, little is known about the behavioral effects of centrally administered 5-HT2 compounds in animal models of anxiety.
  
  
  OBJECTIVE
  The current study was performed to: (1) further investigate the effects of 5-HT2 receptor activation in rats exposed to the elevated plus-maze (EPM) and the open-field arena, two widely used animal models for studying anxiety and locomotor activity; and (2) evaluate the involvement of the 5-HT2 receptors within the basolateral nucleus of the amygdala (BLA) in the modulation of such effects.
  
  
  METHODS
  In the first experiment, male Wistar rats were exposed for 5 min to the EPM 27 min following intraperitoneal (i.p.) (1.0 ml/kg) injections of the preferential 5-HT2C receptor agonist 6-chloro-2[1-piperazinyl]pyrazine (MK-212) at doses of 1.0, 2.0, or 4.0 mg/kg. Control animals were injected with saline. The percentage of open-arm entries and the percentage of time spent in these arms were employed as anxiety indexes, whereas the number of closed-arm entries was calculated as indicative of locomotor activity. In the second experiment, rats were exposed for 10 min in an open-field arena to further assess the interference of the same MK-212 doses upon locomotor activity. In Experiment 3, rats were microinjected (0.2 microl) either with the mixed 5-HT 2A/2C receptor antagonist ritanserin (0.5, 1.25, 2.5, and 5.0 microg) or its vehicle into the BLA 12 min following i.p. injections of saline or the intermediate dose of MK-212 (2.0 mg/kg). Fifteen minutes later, each animal was exposed to the EPM as before.
  
  
  RESULTS
  Whereas the highest dose of MK-212 (4.0 mg/kg) induced motor-suppressant effects in both EPM and open-field arena, the intermediate dose of the drug (2.0 mg/kg) reduced open-arm exploration without significantly affecting the number of closed-arm entries. This behavioral profile, consistent with selective anxiogenic effect in the EPM, was dose-dependently prevented by ritanserin microinfusion into the BLA. In saline-pretreated animals, however, ritanserin (all doses) was ineffective.
  
  
  CONCLUSIONS
  MK-212 increases anxiety and decreases locomotor activity. The anxiogenic-like profile of 5-HT2 receptor activation is prevented by the blockade of 5-HT2 receptors within the BLA, which does not have an effect by itself upon basal anxiety levels triggered by the EPM.
authors.affiliation: Laboratório de Psicobiologia, Departamento de Processos Psicológicos Básicos, Instituto de Psicologia, Universidade de Brasília, Brasília, DF, Brazil. apmcruz@unb.br
authors.forename: Antonio Pedro
authors.initials: AP
authors.lastname: de Mello Cruz
authors.forename: Gilson
authors.initials: G
authors.lastname: Pinheiro
authors.forename: Sérgio Henrique
authors.initials: SH
authors.lastname: Alves
authors.forename: Graziela
authors.initials: G
authors.lastname: Ferreira
authors.forename: Marília
authors.initials: M
authors.lastname: Mendes
authors.forename: Letícia
authors.initials: L
authors.lastname: Faria
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Macedo
authors.forename: Vitor
authors.initials: V
authors.lastname: Motta
authors.forename: J
authors.initials: J
authors.lastname: Landeira-Fernandez
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000502:physiology; D016713:Ritanserin / Q000008:administration & dosage / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D011719:Pyrazines; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; C014896:6-chloro-2-(1-piperazinyl)pyrazine