Abstract
It has been proposed that prolonged pharmacologic blockade of specific receptor sites by specific antagonists results in specific denervation hypersensitivity. The exact specificity of such antagonist-induced behavioral hypersensitivity has not previously been investigated. The present study was undertaken to determine whether hypersensitivity induced by a chronic dopamine antagonist (chlorpromazine or haloperidol) and by a serotonin antagonist (methysergide) is specific to their respective agonists or whether the induced physiologic alterations are more generalized. Chlorpromazine, haloperidol, or methysergide was given to guinea pigs daily for 21 days and the subsequent behavioral responses to d-amphetamine, apomorphine, and d,l-5-hydroxytryptophan were observed.
Chronic dopaminergic antagonism resulted in hypersensitivity to dopamine agonism but did not change the response to serotonin agonism as gauged by 5-hydroxytryptophan-induced stereotypy. Chronic serotonin antagonism was shown to result in hypersensitivity to serotonin agonism, which was not associated with any increase in the behavioral response to either direct or indirect dopamine antagonists. These findings indicate that the chronic administration of dopamine and serotonin antagonists results in behavioral hypersensitivity, which is limited to the system antagonized, and that antagonist-induced hypersensitivity involves the transmitter-specific receptors blocked by the antagonist in question.
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Klawans, H.L., D'Amico, D.J., Nausieda, P.A. et al. The specificity of neuroleptic- and methysergide-induced behavioral hypersensitivity. Psychopharmacology 55, 49–52 (1977). https://doi.org/10.1007/BF00432816
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DOI: https://doi.org/10.1007/BF00432816