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A possible neurochemical basis of the central stimulatory effects of pp'DDT
Abstract:
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.
Insights
p,p-DDT exposure in mice caused severe convulsions and significant striatal neurochemical alterations, including increased ammonia and decreased GABA and acetylcholine. Certain barbiturates and aminooxyacetic acid offered protection by modulating these neurochemical changes.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- p,p'-DDT is an organochlorine pesticide known to affect the central nervous system.
- Striatal neurochemical pathways are crucial for motor control and are implicated in convulsive disorders.
Purpose of the Study:
- To investigate the specific striatal neurochemical changes induced by p,p'-DDT exposure in mice.
- To evaluate the modulatory effects of various barbiturates and other agents on p,p'-DDT-induced neurotoxicity and convulsions.
Main Methods:
- Mice were administered a single high dose of p,p'-DDT (600 mg/kg).
- Striatal levels of free ammonia, GABA, and acetylcholine were measured at peak convulsive activity (5 hours post-treatment).
- The effects of phenobarbitone, prominal, primidone, aminooxyacetic acid, hydroxylamine, and pyridoxine on convulsions and neurochemical changes were assessed.
Main Results:
- p,p'-DDT induced severe convulsions, increased striatal free ammonia, decreased GABA, and reduced acetylcholine.
- Phenobarbitone completely prevented convulsions and normalized GABA and acetylcholine levels.
- Aminooxyacetic acid abolished convulsions and normalized acetylcholine while increasing GABA.
- Other agents showed varying degrees of protection or no effect on convulsions and neurochemical profiles.
Conclusions:
- p,p'-DDT-induced neurotoxicity in the striatum involves alterations in ammonia, GABA, and acetylcholine metabolism.
- Barbiturates, particularly phenobarbitone, can effectively counteract p,p'-DDT's neurotoxic effects, suggesting a role for GABAergic and cholinergic systems.
- Increased free ammonia may contribute to p,p'-DDT's stimulatory effects and subsequent GABA reduction.