Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze.
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.
de Mello Cruz
Antonio Pedro
AP
Laboratório de Psicobiologia, Departamento de Processos Psicológicos Básicos, Instituto de Psicologia, Universidade de Brasília, Brasília, DF, Brazil. apmcruz@unb.br
Pinheiro
Gilson
G
Alves
Sérgio Henrique
SH
Ferreira
Graziela
G
Mendes
Marília
M
Faria
Letícia
L
Macedo
Carlos Eduardo
CE
Motta
Vitor
V
Landeira-Fernandez
J
J
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*
D011719:Pyrazines; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; C014896:6-chloro-2-(1-piperazinyl)pyrazine