Potentiation of apomorphine-induced stereotyped behaviour by acute treatment with dopamine depleting agents: a potential role for an increased stimulation of D1 dopamine receptors.

Treatment of mice with reserpine (10 mg/kg, s.c.) and alpha-methylparatyrosine (400 mg/kg) led to the potentiation of stereotyped behaviour, induced by apomorphine (0.37-1.5 mg/kg, s.c.), i.e. to the appearance of licking and gnawing in addition to climbing and sniffing occurring in control mice. Similar results were obtained by combined treatment with SK&F 38393 (30 mg/kg, s.c.) and RU 24926 (15 mg/kg, i.p.). In mice treated with dopamine depleting agents, SCH 23390 (1.25-20 micrograms/kg, s.c.) and metoclopramide (0.62-20 mg/kg, i.p.) antagonized gnawing induced by 0.75 mg/kg (s.c.) apomorphine, at doses significantly larger than those required for the antagonism of climbing and sniffing. The same treatment with reserpine and alpha-methylparatyrosine produced an increased formation of cyclic AMP, induced by SK&F 38393 (10(-8)-10(-4) M), from homogenates of the striatum of the rat. Potentiation of apomorphine-induced stereotyped behaviour and increased SK&F 38393-induced formation of cyclic AMP had similar time-courses with a maximum 18 hr after treatment. These data suggest that the potentiation of apomorphine-induced stereotyped behaviour produced by acute treatment with dopamine depleting agents is at least partly due to an increased activity of the adenylate cyclase linked to D1 dopamine receptors. Finally, a small dose of amisulpride (a discriminant benzamide derivative) potentiated the stereotyped behaviour induced by the combined treatment with SK&F 38393 and RU 24926 in naive mice and, in a more marked manner, in mice treated with dopamine depleting agents; amisulpride did not produce stereotyped behaviour when combined with SK&F 38393 or RU 24926 administered alone.(ABSTRACT TRUNCATED AT 250 WORDS)