Effects of Drugs Acting on Cerebral 5‐hydroxytryptamine Mechanisms on Dopamine‐dependent Turning Behaviour in Mice

Abstract

I 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. 5Systemic 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.

The Influence of Cerebral 5‐hydroxytryptamine on Catalepsy Induced by Brain‐amine Depleting Neuroleptics or by Cholinomimetics

“…Thus, administration of 5-HTP inhibits, while administration of methysergide increases, the production of stereotypies by both amphetamine and apomorphine, the one acting pre-, the other postsynaptically. The circling behaviour produced by apomorphine in rats lesioned in one substantia nigra is increased by treatment with methysergide or PCPA, and diminished by the injection of 5-HTP or tryptophan (Baldessarini, Amatruda, Griffith & Gerson, 1975;Milson & Pycock, 1976). The findings on catalepsy, stereotyped behaviour and rotatory behaviour support the hypothesis that ascending 5-HT neurones modulate the output of the nigrostriatal dopaminergic neurones.…”

Noradrenaline and 5‐hydroxytryptamine modulation of brain dopamine function: implications for the treatment of Parkinson's disease.

“…The interaction between 5HT and dopamine neuronal systems within the nigrostriatal complex is supported by a number of major findings which can be summarized as follows: 1) In mice with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway, the administration of 5HT precursors such as Ltryptophan or 5-hydroxytryptophan increased brain 5HT levels and decreased circling behaviour induced by both apomorphine and amphetamine (Milson & Pycock, 1976; Figure 1). In contrast, depletion of cerebral 5HT using p-chloro-phenylalanine decreased brain 5HT and increased both amphetamine and apomorphine-induced circling behaviour.…”

The Influence of L‐tryptophan and Monoamine Oxidase Inhibitors on Catecholamine Metabolism in Rat Brain

“…The fact that the concentration of noradrenaline did not fall and that the concentration of dopamine rose after L-tryptophan implies that, if the raised metabolites are a consequence of the release of dopamine and noradrenaline by 5-HT or tryptamine (Marsden & Curzon, 1978) then synthesis of the amines must have increased to keep pace with this release. Previous workers (Milson & Pycock, 1976) have shown that when 5-HT turnover is increased either by administration of tryptophan or 5-hydroxytryptophan there is an inhibition of contralateral turning induced by apomorphine in rats with unilateral lesions in the dopaminergic system (Ungerstedt, 1971). This inhibition of turning could be accounted for by release of dopamine from the intact striatal dopaminergic neurones which counteracted the turning induced by apomorphine via the supersensitive receptors.…”