Effects of drugs acting on cerebral 5-hydroxytryptamine mechanisms on dopamine-dependent turning behaviour in mice.
1. The effects of drugs acting on cerebral 5-hydroxytryptaminergic mechanisms on drug-induced turning behaviour in mice with unilateral destruction of nigro-striatal dopaminergic nerve terminals have been studied. 2. Administration of L-tryptophan (400 mg/kg) or 5-hydroxytryptophan (200 mg/kg) increased brain 5-hydroxytryptamine and decreased the turning induced by both apomorphine (2 mg/kg) and amphetamine (5 mg/kg). 3. Parachlorophenylalanine (3 X 500 mg/kg) decreased brain 5-hydroxytryptamine and increased both apomorphine and amphetamine-induced circling behaviour. 4. Varying the protein content of dietary intake significantly altered brain 5-hydroxytryptamine and tryptophan levels, spontaneous locomotor activity and amphetamine-induced circling behaviour in these mice. 5. Systemic administration of methysergide (0.5-4 mg/kg), lysergic acid diethylamide (0.025-0.2 mg/kg), cyproheptadine (2.5-20 mg/kg) or clomipramine (0.6-20 mg/kg) produced no consistent effect on drug-induced turning behaviour. 6. The results suggest that circling behaviour due to striatal dopamine receptor stimulation is depressed by an elevation of brain 5-hydroxytryptamine and enhanced by a reduction in brain 5-hydroxytryptamine. 7. The possible physiological relationship between dopamine and 5-hydroxytryptamine neurones in the basal ganglia is discussed.
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001519:Behavior / Q000187:drug effects*; D002997:Clomipramine / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D004032:Diet; D004298:Dopamine / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects*; D014364:Tryptophan / Q000494:pharmacology
D000662:Amphetamines; D003533:Cyproheptadine; D012701:Serotonin; D014364:Tryptophan; D008238:Lysergic Acid Diethylamide; D001058:Apomorphine; D002997:Clomipramine; D010134:Fenclonine; D004298:Dopamine; D008784:Methysergide