p,p'-DDT myoclonic/epileptic model: serotonin receptor binding and behavioral studies in the rat.
An abnormality of serotonergic neurotransmission has been hypothesized in p,p'-DDT intoxication to explain myoclonus and the antimyoclonic properties of 5-hydroxytryptophan (5-HTP). To study the role of serotonin (5-HT) receptors in myoclonus induced by p,p'-DDT in the rat, we performed time-course and dose-response studies of the effects of p,p'-DDT on behavior and regional 5-HT1 and 5-HT2 binding sites. At a time when low dose (80 mg/kg) p,p'-DDT elicited stimulus-sensitive and spontaneous myoclonus, there were no significant changes in Bmax or Kd 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) binding sites in cortex but not in brainstem or spinal cord and had no effect on antagonist-labelled 5-HT2 sites. In naive frontal cortex in vitro, 1 microM p,p'-DDT displaced neither [3H]5-HT or [3H]ketanserin specific binding. Lesions of central indoleamine neurons made with 5,7-dihydroxytryptamine 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 percent of the rats. This is the first report of 5,7-DHT-induced attenuation in the p,p'-DDT myoclonic model.
Pranzatelli
M R
MR
Department of Neurology, George Washington University, Washington, D.C.
Tailor
P T
PT
Pluchino
R
R
Gonzales
W
W
Simmens
S
S
D015116:5,7-Dihydroxytryptamine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003634:DDT / Q000633:toxicity*; D004195:Disease Models, Animal; D004831:Epilepsies, Myoclonic / Q000139:chemically induced* / Q000378:metabolism / Q000523:psychology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced
D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine; D003634:DDT