Differential effects of 5-hydroxytryptamine antagonists on behaviors resulting from activation of different pathways arising from the raphe nuclei

Autor: Mark Segal, Marta Weinstock
Rok vydání: 1983
Předmět:
Zdroj: Psychopharmacology. 79(1)
ISSN: 0033-3158
Popis: A serotonin syndrome of reciprocal forepaw treading, lateral head weaving, rigid tail, hind limb abduction, tremor, and hyperreactivity to touch and sound was produced in the rat by the injection of p-methoxyphenethylamine (PMPEA) or 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). The former agent acts by releasing serotonin (5-HT) from nerve terminals, since its effects are prevented by pretreatment with PCPA or fluoxetine, while 5-MeODMT acts directly on 5-HT receptors. The syndrome results from activation of 5-HT neurones in the lower brain stem and spinal cord. Only dl-propranolol and pindolol (1–5 mg/kg) significantly reduced most of the components of the syndrome. Haloperidol (0.1–1 mg/kg), metoprolol, atenolol, and butoxamine (10–20 mg/kg) were inactive. Metergoline (1 mg/kg), methysergide (5–10 mg/kg), and cyproheptadine (10 mg/kg) markedly potentiated all components of the syndrome produced by PMPEA. The inhibition of forward locomotor hyperactivity (LMA) induced in the rat after larger doses of amphetamine was prevented by p-chlorophenylalanine pretreatment, while stereotyped behavior still remained. This supports previous data showing that release of 5-HT from mesolimbic neurones is partly responsible for inhibition of LMA. In contrast to the action on the PMPEA syndrome, methysergide, metergoline, cyproheptadine in addition to propranolol and pindolol, increased LMA induced by amphetamine, while butoxamine and metoprolol were inactive. It is concluded that the 5-HT receptors subserving inhibition of LMA in the mesolimbic area differ from those mediating the serotonin syndrome.
Databáze: OpenAIRE
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