The effect of acute and chronic desipramine (10 mg/kg) and citalopram (10 mg/kg) treatment on rat exploratory behavior in the recently developed exploration box test was studied on 5 consecutive days. Acute desipramine but not citalopram treatment decreased the time spent exploring, the number of line crossings, rears, investigative approaches, entries into the large arena, and sum of exploratory events. After 3 weeks of pretreatment, both desipramine and citalopram attenuated rat exploratory behavior, whereas the number of entries into the large arena was unchanged. In the open field test, acute desipramine or citalopram treatment (5, 10, 15 mg/kg) attenuated rat exploratory behavior in a dose-dependent manner. In the subsequent rota-rod test, neither desipramine nor citalopram treatment (0-20 mg/kg) impaired motor performance capacity. In an additional experiment, [3H]raclopride binding was unchanged after single as well as 3 weeks of desipramine or citalopram treatment in the rat brain neostriatum. Our experiments demonstrate that acute citalopram treatment in the open field test and chronic citalopram treatment in the exploration box test attenuate rat exploratory behavior, but these effects may not be implicated with enhanced anxiety or changed dopamine D2 receptor characteristics.