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)
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Laboratoire de Physiologie (U.A. CNRS 1170), U.E.R. de Médecine-Pharmacie de Rouen, Saint Etienne du Rouvray, France.
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000077582:Amisulpride; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D018492:Dopamine Antagonists; D004357:Drug Synergism; D066298:In Vitro Techniques; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D008787:Metoclopramide / Q000494:pharmacology; D051379:Mice; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*; D013469:Sulpiride / Q000031:analogs & derivatives / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D018492:Dopamine Antagonists; D008781:Methyltyrosines; D010627:Phenethylamines; D011954:Receptors, Dopamine; D019805:alpha-Methyltyrosine; C025254:RU 24926; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D000077582:Amisulpride; D012110:Reserpine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D008787:Metoclopramide; D001058:Apomorphine