Monoamine systems, effects exposure

V. Nair, Prenatal exposure to drugs Effect on the development of brain monoamine systems, in A. Vernadakis and N. Veiner (Eds.), Drugs and the Developing Brain, Plenum Press, New York, 1974, pp. 171-194. 

The effects of developmental exposure of pyrethroids on the dopaminergic system, which is considered to be related to behavior, were examined in several studies, but inconsistent results were obtained. Administration of deltamethrin between gestation day 6 and 15 induced increase of DOPAC (dopamine metabolite) levels in adult rats [54]. Exposure of fenvalerate on gestation day 18 and during postnatal days 2-5 produced no effect on monoamine levels on postnatal day 21 [55]. Gestational and lactational exposure to fenvalerate decreased and increased 3H-spiroperidol binding in striatum after development, respectively, whereas only lactational exposure of cypermethrin induced increase in 3H-spiroperidol binding [56]. 

Antidepressant drugs, by contrast, require long-term administration for their therapeutic effects to become evident. Thus, it is clear that the acute actions of these drugs, which are most often to enhance synaptic levels of monoamines, are not sufficient in themselves to mediate their therapeutic effects. Neither is the effect of increased monoamines on postsynaptic second messenger systems, which occurs relatively quickly as well, adequate to account for the therapeutic actions of antidepressants. The most obvious explanation, then, is that molecular adaptations in response to chronic exposure to these drugs are what underlie their therapeutic effects. Consistent with this idea, several hypotheses as to the nature of the relevant molecular adaptations have been proposed. Two models focus on adaptations of the 5-HTia receptor. One theory proposes that desensitization of presynaptic somatodendritic 5-HTia autoreceptors is responsible for the therapeutic action... 

Animal studies have detected a variety of pharmacological and biochemical changes in response to chlordimeform exposure. The cause of death following acute exposure appears to be cardiovascular collapse. Chlordimeform interacts directly with and inhibits a2-adrenergic receptors in mammalian systems. Lethal doses of chlordimeform cause decreases in cardiac contractility and peripheral resistance resulting in severe hypotension. Respiratory arrest also occurs but is thought to be secondary to the cardiovascular effects. The effects of chlordimeform on the cardiovascular system share similarities with those seen with local anesthetics such as procaine. Chlordimeform also inhibits monoamine oxidase and acts as an uncoupler of oxidative phosphorylation. 

Other Effects of Cadmium on the Central Nervous System. Cadmium may affect the activity of certain enzymes in the brain. Adenylate cyclase activity in the rat cerebrum, cerebellum, and brain stem vv as inhibited in vitro by micromolar concentrations of cadmiumMonoamine oxidase, which is involved in the catabolism of transmitter monoamines, was also lowered in activity by cadmium in vitro A comparative study of the effects of cadmium and zinc on cholinesterase activity in the brain showed that cadmium activated cholinesterase, whereas zinc reduced this enzyme after acute intoxication. Following chronic exposure to both metals, the cholinesterase activity was not significantly altered. ... 

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