Neuroendocrine effects of neuropsychotropic drugs and their possible influence on toxic reactions in animals and man -- the role of the dopamine-prolactin system.

As an example for the importance of the neuroendocrine system in the toxicological evaluation of neuropsychotropic drugs, the influence of functional dopaminergic agonists and antagonists on the secretion of prolactin is studied. In rats, all functional dopamine antagonists (reserpine alone or combined with alpha-methyl-p-tyrosine or benserazide, haloperidol, spiroperidol, sulpiride) increased serum PRL levels. Dopaminergic agonists (apomorphine, piribedil, d-amphetamine, L-DOPA, and the ergot derivatives bromocriptine and lisuride) all caused a decrease of serum prolactin levels. The same effect could be observed also after treatment with other ergot derivatives such as d-LSD, methergoline, methysergide and ergotamine. Also in this case, the prolactin-lowering effect seems to be related to dopaminergic activity. This was suggested by the inhibitory effect of pretreatment with the dopamine antagonist spiroperidol or with sulpiride on the prolactin-lowering effect of lisuride. In dogs, thyrotropin releasing hormone (TRH) increased and lisuride decreased serum prolactin levels determined with a new radioimmunoassay. As an example for the situation in humans, the effects of the dopamine antagonist sulpiride and of the dopamine agonist bromocriptine were described. The prolactin levels were higher in the presence of estrogens. The relevance of these neuroendocrine effects of neuropsychotropic drugs on physiological systmes in animals and man is discussed.