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Peripheral serotonin antagonists: Failure to antagonize serotonin in brain areas receiving a prominent serotonergic input

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Summary

It has been suggested that drugs block the effects of serotonin (5-HT) in the brain based on (1) the ability to block the effects of 5-HT on smooth muscle and on invertebrate neurons (e.g., cinanserin, cyproheptadine, methysergide [UML], and metergoline [MCE]) and (2) the ability to block certain gross electrophysiological effects of 5-hydroxytryptophan (e.g., methiothepin). Although these “antagonists” are often assumed to block all 5-HT receptors in the CNS, the ability of these drugs to block 5-HT at documented 5-HT synapses in the brain has not been thoroughly tested. Since 5-HT may produce either excitation or inhibition, these antagonists were evaluated with respect to both types of responses. Only inhibition is produced by 5-HT on cells in areas receiving a heavy serotonergic input (e.g., ventral lateral geniculate, optic tectum and amygdala) as determined by fluorescent histochemistry. Raphe cells, virtually the only 5-HT-containing neurons in the CNS, are also inhibited by 5-HT. Cells in the reticular formation, an area which receives little or no 5-HT input may be either excited or inhibited by 5-HT. The five putative antagonists do not block the inhibitory response to 5-HT in any of these areas. The excitatory response to 5-HT in the reticular formation can be blocked by the putative antagonists. However, the failure of these compounds to block 5-HT in any of the three areas tested that receive a heavy serotonergic input casts doubt on the assumption that any one of these compounds is a universal central 5-HT antagonist.

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  1. H. J. Haigler

    Present address: Department of Pharmacology, Emory University, 30322, Atlanta, GA, USA

Authors and Affiliations

  1. Departments of Psychiatry and Pharmacology, Yale University School of Medicine and the Connecticut Mental Health Center, New Haven, Connecticut, USA

    H. J. Haigler & G. K. Aghajanian

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Haigler, H.J., Aghajanian, G.K. Peripheral serotonin antagonists: Failure to antagonize serotonin in brain areas receiving a prominent serotonergic input. J. Neural Transmission 35, 257–273 (1974). https://doi.org/10.1007/BF02205223

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  • DOI: https://doi.org/10.1007/BF02205223

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