Synthesis and utilization of neurotransmitters: actions of subconvulsant doses of hexachlorocyclohexane isomers on brain monoamines.

We have developed a model for the treatment of data of concentration of brain neurotransmitters (particularly serotonin and the catecholamines), in which the changes induced by any given treatment on the neurotransmitter (NT) and its main metabolite (ME) are converted into 2 new parameters named S and U, that are related to the modifications in the synthesis (S) and utilization (U) of the neurotransmitter elicited by the treatment. Using this model we have studied the effect of subconvulsant doses of lindane and other hexachlorocyclohexane isomers (alpha, beta and delta) on brain monoaminergic systems. The results obtained indicate that serotonergic activity is increased in cell bodies (dorsal raphe) as well as in regions rich in nerve terminals after treatment with lindane. Also, the activity of dopaminergic neurons is increased in the substantia nigra. These results are in agreement with the proposed role of lindane as a "picrotoxinin-like" substance acting as an antagonist at the GABA-A receptor complex and thus impairing the inhibitory tone exerted by GABA on a variety of neurons (serotonin in raphe nuclei and dopamine in substantia nigra).