Erowid References Database
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Milson JA, Pycock CJ.
“Effects of Drugs Acting on Cerebral 5-Hydroxytryptamine Mechanisms on Dopamine-Dependent Turning Behavior in Mice”.
Brit.J.Pharmacol.. 1975;56(1):77-85.
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Abstract
The effects of drugs acting on cerebral 5-hydroxytryptaminergic mechanisms on amphetamine (AM) and apomorphine (APO) induced turning in mice with unilateral lesions of the nigro-striatal dopamine terminals (NSDT) were studied. Methods Unilateral destruction of NSDT in Swiss S strain mice was achieved by direct injection of 6-hydroxydopamine. Mice were given i.p. 5-hydroxytryptophan (5-HTP; Sigma), L-tryptophan (Try; Koch Light), p-chlorophenylalanine (PCPA; Sigma), LSD (Sandoz), clomipramine HCl (Geigy), methysergide (Sandoz) or cyproheptadine (Merck-USA). Mice were later given d-AM (SK+F) or APO (Evans ['edical) and the number of complete revolutions made during a 1 min period recorded. Some mice were fed a low or a bigh protein diet. Mice were killed at intervals and forebrains removed, and analyzed for serotonin (5-HT) content. Results 5-HTP (200 mg/kg) produced a 200% rise in forebrain 5-HT and a small decrease (800f control) in rate of turning to APO bu t a greater decrease (400f control) in turning to AM. Try at 400 mg/kg increased brain 5-HT levels to 1500f control and decreased turning to both APO and AM to about 700f control. PCPA in 3 daily doses of 500 mg/kg depleted brain 5-HT levels to 190f contr and induced an insignificant increase in rate of turning to APO (1170f control) but a significant increase in AM-induced turning (1420f control). Methysergide, LSD, cyproheptadine and clomipramine had no consistent effect on drug-induced turning. Changes in dietary protein significantly altered brain 5-HT and try levels, spontaneous motor activity and AM-induced turning. Conclusions Circling behavior due to NSD receptor stimulation is depressed by an increase in brain 5-HT and enhanced by a decrease in brain 5-HT.
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