Stewart RM, Growdon JH, Cancian D, Baldessarini RJ.
“5-Hydroxytryptophan-Induced Myoclonus: Increased Sensitivity to Serotonin after Intracranial 5,7-Dihydroxytryptamine in the Adult Rat”.
Neuropharmacology. 1976;15(8):449-55.
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Abstract
5-Hydroxytryptophan (5-HTP)-induced myclonus in intracisternal 5,7-dihydro-ytryptamine (5,7-DHT)-and systemic desmethylimipramine (DMI)-treated rats was studied. Methods Male Sprague Dawley 190-210 rats were neurochemically lesioned with intracisternal 5,7-DHT (Aegis) as previously described. Desmethylimipramine (DMIl (Norpramin, Lakeside) (25 mg/kg i.p. was injected 4hr and 1 hr before 5,7-DHT (200 mcg) and rats were tested 12 hr later. They were observed for 20 sec periods at 5 and 15 min after injection of L-5HTP (Calbiochem) (65 mg/kg i.p.) and at 15 min intervals until tremor, ataxia and myclonic activity stopped. Some drugs were given alone or 15 min to 2 hr before 5-HTP (65 mg/kg i.p.): n-methyl-p-tyrosine (50 mg/kg), apomorphine (Merck) (2 mg/kg), atropine (Matheson Coleman + Bell) (1 mg/kg), bicuculline (K+Kl (3 mg/kg), 2bromolysergic acid (Sandoz) (0.5 mg/kg), chlorimipramine (Anafranil, CIBA-Geigy) (15 mg/kg), haloperidol (Haldol, McNeil) (10 mg/kg), imipramine (Tofranil) (35 mg/kg), L-dopa (Sigma) (500 mg/kg) L-tryptophan (100-300 mg/kg), LSD (0.1 mg/kgl, methysergide (Sansert) (1 mg/kg), pargyline (Eutonyl, Abbott) (100 mg/kg), para-ehlorophenylalanine) (300 mg/kg), pchlorophenyl-GABA (Lioresal) (5 mg/kg), phenoxybenzamine (Dibenzyline, SK+F) (10 mg/kg), phentolamine (Regitine) (5 mg/ kg), physostigmine (1 mg/kgl, propranolol (luderal, Ayerst) (0.2 mg/kg), Ro4-4602 (10-200 mg/kgl and serotonin (65 mg/kg). 5uL 1 5-Hr1P produced tremor and myclonus in animals treated with 5,7-DHT and DMI but not in controls. The behavioral syndrome reached a maximum at 10-14 days and lasted at least 16 wk after 5,7-DHT. The myclonic syndrome was potentiated by pargyline but inhibited by LSD, 2-bromolysergic acid, methysergide and Ro4-4602. The myclonus following 5-HTP was not reproduced or affected by drugs which increase or decrease the effects of other neurotransmitters e.g dopamine, norepinephrine, acetylcholine or GABA. Conclusions The 5-HTP induced myoclonus following 5,7-DHT + DMI may reflect pre- or postsynaptically mediated sensitivity to 5-HT.
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