Abstract
The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats) and low (spontaneously hypertensive rats, SHR) anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing) increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing) failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage) was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.
Highlights
Reports that the acute peripheral administration of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine promotes or exacerbates anxietyrelated behaviors in laboratory animals and humans, respectively, have led to the suggestion that these receptors - at least those located in the hippocampus [1] - play a role in the modulation of anxiety
Studies comparing the anxiolytic effects of SB 206553 with those of standard anxiolytics, e.g., benzodiazepines, have concluded that SB 206553 exerts anxiolytic effects in unconditioned and conditioned tests [7,8]
In a study aimed at comparing several components of central serotonergic systems in rat strains respectively displaying high (Lewis rat) and low anxiety in the elevated plus-maze, it was found that the 5-HT2B/2C receptor-mediated hypolocomotor effect of mCPP [9] was of similar potency in these two strains [10]
Summary
Reports that the acute peripheral administration of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (mCPP) promotes or exacerbates anxietyrelated behaviors in laboratory animals and humans, respectively, have led to the suggestion that these receptors - at least those located in the hippocampus [1] - play a role in the modulation of anxiety (for a review, see 2). The hypothesis that differences in anxiety between SHR and Lewis rats are mediated by 5-HT2B/2C receptors (see above) could not be examined because the high anxiety levels of Lewis rats prevented any inter-strain analysis of the anxiogenic effects of mCPP in the elevated plus-maze [10]. In the present study we examined the hypothesis that the control exerted by 5HT2B/2C receptors on anxiety-related behaviors is of greater impact in Lewis rats than in SHR. To this end, we assessed the behavioral effects of SB 206553 administration to Lewis rats and SHR exposed to an elevated plus-maze test, and compared these effects to those elicited by the standard anxiolytic, diazepam [11]
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