A possible neurochemical basis of the central stimulatory effects of pp'DDT.
The striatal neurochemical changes induced by pp'DDT (600 mg/kg) in mice were: an increase in the concentration of free ammonia, a decrease in the level of GABA and a reduction in the level of acetylcholine. These changes were maximal 5 h after treatment with pp'DDT, when the animals developed 'severe' convulsions. The convulsions and striatal neurochemical changes were modified to different degrees by barbiturates. Phenobarbitone protected all the animals from pp'DDT-induced convulsions. The levels of striatal acetylcholine and GABA in these animals were within normal limits. Prominal reduced the severity of convulsions in pp'DDT-treated animals. The levels of striatal acetylcholine and GABA were significantly lower than control values in these animals. Primidone neither modified the convulsions nor the striatal neurochemical changes in pp'DDT-treated animals. The increase in the concentration of free ammonia, in pp'DDT-treated animals, was not modified by barbiturates. Aminooxyacetic acid raised the GABA level above normal and abolished the convulsions in pp'DDT-treated animals; the level of acetylcholine was within normal limits in these animals. Hydroxylamine produced a similar but less marked effect. Pyridoxine had no effect on convulsions or striatal neurochemical changes induced by pp'DDT. The increase in the concentration of free ammonia in pp'DDT-treated animals was not modified by these agents. It is likely that pp'DDT produced stimulatory effects by increasing the concentration of free ammonia which may be involved in reducing the level of GABA, while changes in the level of acetylcholine may be an effect of pp'DDT-induced convulsions.
D000109:Acetylcholine / Q000378:metabolism; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003634:DDT / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006898:Hydroxylamines / Q000494:pharmacology; D008297:Male; D008618:Mephobarbital / Q000494:pharmacology; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology; D011324:Primidone / Q000494:pharmacology; D011736:Pyridoxine / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D006898:Hydroxylamines; D011324:Primidone; D000625:Aminooxyacetic Acid; D005680:gamma-Aminobutyric Acid; D008618:Mephobarbital; D000641:Ammonia; D003634:DDT; D011736:Pyridoxine; D000109:Acetylcholine; D010634:Phenobarbital