Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonistSB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze

The 5-HT2B/2C receptor antagonist SE 206553 exerts anxiolytic effects in ra t models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SE 206553 effects in rat strains di splaying different levels of anxiety. Herein, the effects of SE 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the ref erence anxiolytic, diazepam, in two rat strains respectively displaying hig h (Lewis rats) and low (spontaneously hypertensive rats, SHR) anxiety. Diaz epam (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, SE 206553 (1.25, 2.5, or 5 mg/kg; 30 min before resting) fa iled 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 nonsele ctive 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 SE 206553 in Lewis rats and SHR, respectively. Comp ared with SHR, Lewis rats may display a lower response to benzodiazepine-me diated effects and a more efficient control of locomotor activity by 5-HT2B /2C receptors.