P,P'-DDT MYOCLONIC EPILEPTIC MODEL - SEROTONIN RECEPTOR-BINDING AND BEHAVIORAL-STUDIES IN THE BAT/

An abnormality of serotonergic neurotransmission has been hypothesized in p,p'-DDT intoxication to explain myoclonus and the antimyoclonic p roperties of 5-hydroxytryptophan (5-HTP). To study the role of seroton in (5-HT) receptors in myoclonus induced by p,p'-DDT in the rat, we pe rformed time-course and dose-response studies of the effects of p,p'-D DT on behavior and regional 5-HT1 and 5-HT2 binding sites. At a time w hen low dose (80 mg/kg) p,p'-DDT elicited stimulus-sensitive and spont aneous myoclonus, there were no significant changes in B-max or K-d of 5-HT1A, 5-HT1B, 5-HT1C sites in cortex, striatum, brainstem or spinal cord, agonist- or antagonist-labelled 5-HT2 sites in cortex, or 5-HT uptake sites. High dose p,p'-DDT (1000 but not 500 mg/kg), which also induced convulsions, only slightly increased 5-HT1 (unsubtyped) bindin g sites in cortex but not in brainstem or spinal cord and had no effec t on antagonist-labelled 5-HT2 sites. In naive frontal cortex in vitro , 1 mu M p,p'-DDT displaced neither [H-3]5-HT or [H-3]ketanserin speci fic binding. Lesions of central indoleamine neurons made with 5,7-dihy droxytryptamine significantly prolonged the latency and attenuated the severity of p,p'-DDT behavioral abnormalities, increasing the dose of p,p'-DDT which induced myoclonus (MD50) or convulsions (CD50) in 50 p ercent of the rats. This is the first report of 5,7-DHT-induced attenu ation in the p,p'-DDT myoclonic model. (C) 1994 Intox Press, Inc.