Locomotor Behaviour of Selective Dopamine Agonists in Mice: Is Endogenous Dopamine the Only Catecholamine Involved?

Abstract

Abstract The purpose of the study was to determine the effect alone and in combination of the selective dopamine (DA) agonists SKF 38393 (D1-) and B-HT 920 (D2-) on the locomotor activity of reserpine pretreated mice (5 mg kg−1 i.p.). After 4 h, reserpine-B-HT 920 (up to 20 mg kg−1 s.c.) did not induce locomotor activity whereas SKF 38393 was markedly effective at high doses (≥ 30 mg kg−1 s.c). In contrast, at 24 h, reserpine-B-HT 920 (0·2–6 mg kg−1 s.c.) elicited considerable locomotor activity and SKF 38393 (1–100 mg kg−1 s.c.) was effective at lower doses when compared with the corresponding 4 h reserpine experiments. When, however, these animals additionally received α-methyl-p-tyrosine (αMPT; 300 mg kg−1 i.p., at 4 h before the DA agonists) neither B-HT 920 (0·2–20 mg kg−1 s.c.) nor SKF 38393 (1–100 mg kg−1 s.c.) had an effect of their own. When B-HT 920 was tested in the presence of a fixed-dose of SKF 38393 (10 or 3 mg kg−1 s.c., combination experiments) B-HT 920 (0·6–20 mg kg−1 s.c.) induced considerable locomotor activity at 4 h post reserpine. At 24 h post reserpine the dose-response curve of B-HT 920 (0·06–20 mg kg−1 s.c.) was shifted to the left and the maximum effect was greatly increased. When additional αMPT was given, the dose response curve was the same but the maximum effect was markedly reduced. When SKF 38393 was tested in the presence of a fixed-dose of B-HT 920 (2 mg kg−1 s.c.; combination experiments) this resulted in a dose response curve in the range of 0·3–10 mg kg−1 s.c. at 4 h post reserpine. At 24 h post reserpine the curve shifted to the left by approximately a factor of 30 (0·1–3 mg kg−1 s.c.) and the maximum effect was markedly increased. Additional αMPT shifted the curve to the right by a factor of approximately 30 without a substantial change in the maximum effect. It is concluded that simultaneous stimulation of D1- and D2- receptors is necessary to elicit locomotor activity in mice. From dose response analysis of experiments with additional αMPT it is furthermore concluded that endogenous noradrenaline may play an additional modulatory role.