DDT-induced myoclonus: serotonin and alpha noradrenergic interaction.
p,p'-DDT (600 mg/kg) produces myoclonic activity in mice which can be reduced by L-5-hydroxytryptophan (L-5HTP) (200 mg/kg), H75/12 (25 mg/kg), serotonin uptake blockers and two alpha-receptor blockers, phenoxybenzamine (5 mg/kg) and trazodone (5 mg/kg). Decreasing endogenous brain serotonin by pretreatment with p-chlorophenylalanine (400 mg/kg i.p.) blocked the antimyoclonic action of all of these drugs except L-5HTP. Seven other alpha-receptor blockers (phentolamine, tolazoline, yohimbine, azapetine, aceperone, nicergoline and prazosin) potentiated the antimyoclonic activity of a small dose of L-5HTP (50 mg/kg) in this animal model. We postulate that an alpha noradrenergic inhibitory synapse may be located in the neural circuit connecting a serotonergic neuron to the final motor response (p,p'-DDT-induced myoclonus).
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003634:DDT / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009207:Myoclonus / Q000139:chemically induced* / Q000503:physiopathology; D009638:Norepinephrine / Q000502:physiology*; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D012702:Serotonin Antagonists; D012701:Serotonin; D006916:5-Hydroxytryptophan; D003634:DDT; D009638:Norepinephrine