Abstract
Buspirone, a drug with high affinity for serotonin 1A receptors, was studied for its ability to reduce rats' immobility in the forced swimming test when injected systematically or into the nucleus raphe dorsalis (DR). Between 0.1 and 10 mg/kg buspirone had no effect on rats' immobility when injected systemically as a single dose or as a 3-injection course during 24 hours. Direct injection of 1 and 5 ug/0.5 μl buspirone in the DR significantly reduced the duration of immobility without changing rats' activity in an open field. The anti-immobility effect of 1 μg/0.5 μl buspirone in the DR was completely prevented by injecting 2.5 μg (-)-propranolol in the same area. Oral administration of 0.3–1.0 mg/kg 1-(2-pyrimidinyl)piperazine (1-PP), one of the main metabolites of buspirone, and 0.3–3.0 mg/kg s.c. idazoxan, two substances with alpha 2 adrenergic blocking properties, completely antagonized the effect of 0.25 mg/kg s.c. 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), an agent with selective affinity for serotonin 1A receptors. The anti-immobility effect of an infusion of 1 μg/0.5 μl buspirone or 8-OH-DPAT in the DR was also antagonized by 1 mg/kg p.o. 1-PP. The results suggest that buspirone possesses potential antidepressant properties but its effect may be masked in certain tests by its metabolite, 1PP, through its alpha 2 adrenergic blocking activity.
Published Version
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