Effects of chronic treatments with amineptine and despiramine on motor responses involving dopaminergic systems

The acute effects of increasing doses of the antidepressant drugs amineptine (5–40 mg/kg, IP) and desipramine (5–20 mg/kg IP) were studied in mice on three parameters of the activity (the horizontal activity, the vertical activity and the number of small movements without displacement) measured in a computerized Digiscan actimeter. The horizontal and vertical activities were dose dependently and similarly increased by acute amineptine, whereas the number of movements without displacement was increased up to 10 mg/kg with no further significant modification up to 40 mg/kg; in contrast, all three parameters were reduced in an identical manner by desipramine. The changes in the responses to the selective D-1 dopamine (DA) receptor agonist SK&F 38393 (1.87–30 mg/kg, SC), to the selective D-2 DA receptor agonist LY 171555 (0.1–1.6 mg/kg, SC) and to the selective DA uptake inhibitor GBR 12783 (1.25–20 mg/kg, IP) were measured on the three parameters of activity in mice chronically treated with amineptine (20 mg/kg, IP twice daily during 15 days) or by desipramine (10 mg/kg, IP, twice daily during 15 days). The chronic treatments with amineptine or desipramine did not modify the motor stimulant effects GBR 12783 and of SK&F 38393 on the three parameters (excepted for a slight modification of the horizontal activity for 7.5 mg/kg SK&F 38393 in mice chronically treated with amineptine). In contrast, the motor inhibitory effects of the lowest doses of LY 171555 (0.1–0.4 mg/kg) were strongly reduced in mice chronically treated with amineptine or desipramine but only on the horizontal activity with no change on the vertical activity and on the number of small movements without displacement. These data indicate that, as in chronic treatment with typical antidepressant drugs like desipramine, chronic treatment with amineptine alters selectively the sedative effects induced by stimulation of D-2 DA autoreceptors in the mesolimbic dopaminergic area involved in the horizontal (locomotor) activity.