The effects of 5-HT 1B characterizing agents in the mouse elevated plus-maze

Abstract

Although the serotonergic system has been implicated in the modulation of anxiety states, the specific receptor subtypes that mediate these states require clarification. The effects of drugs that act preferentially at 5-HT 1B receptors were evaluated on the behavior elicited in the elevated plus-maze, an animal model of anxiety. Variations in the intensity of light affected mouse behavior in the plus-maze; lower light intensity increased the entries to and time spent on the open arm in a manner similar to that seen with stress-attenuating circumstances. Opposite effects were observed in high light-intensity, similar to effects seen under elevated stress conditions. Chlordiazepoxide produced increased entries and time spent on the open arm, whereas pentylenetetrazol (PTZ) produced opposite effects. The preferential 5-HT 1B agents TFMPP and mCPP exhibited a profile similar to PTZ. The effects of TFMPP in the plus-maze were reversed by chlordiazepoxide, but not by the benzodiazepine receptor antagonist flumazenil, which suggests that this effect is not directly mediated by benzodiazepine receptors. The decreased entries and time spent on the open arm of the maze following TFMPP or mCPP administration was possibly mediated by an antagonistic action at 5-HT 1B receptors, since this effects was reversed by the selective 5-HT 1B agonist CGS 12066B. The present study further demonstrates the utility of mouse behavior in the elevated plus-maze as a model for identifying anxio-modulatory substances.