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Possible involvement of the central dopaminergic system in the antireserpine effect of LSD

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Abstract

Both LSD and apomorphine produced hyperactivity in reserpine-treated mice, LSD being more potent and longer-acting than apomorphine. 2-Brom LSD and the serotonin (5-HT) receptor agonist quipazine were ineffective in reversing reserpine sedation. Treatments with phenoxybenzamine and methysergide failed to block the stimulant effects of either LSD or apomorphine, demonstrating the noninvolvement of 5-HT or norepinephrine (NE) receptors in their action. The ineffectiveness of α-methyl-p-tyrosine in modifying the stimulant effects of LSD and apomorphine indicated a probable direct stimulant effect of these two drugs on the dopamine (DA) receptors. Low doses of chlorpromazine, haloperidol, or pimozide blocked the effects of apomorphine in reserpinized mice. Although these neuroleptics significantly reduced the effects of LSD, they failed to block completely the LSD effects even at higher doses. Apomorphine reduced the α-methyl-p-tyrosine-induced depletion of DA in the whole brain of mice, but LSD failed to do so. From these findings it is postulated that apomorphine acts as a direct DA receptor agonist, and that LSD may act directly on a site structurally closely related to DA receptor, but not necessarily identical with it. Repeated treatments with LSD did not lead to development of tolerance to its locomotor effects in reserpinized mice. Moreover, mescaline and psilocybin, which are known to exhibit cross-tolerance to LSD, failed to produce LSD-like effects in reserpine-treated mice. The effects of LSD on the DA or a related site probably are not solely responsible for its psychotomimetic effects.

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Authors and Affiliations

  1. Psychopharmacology Research Laboratory, and Neuropharmacology Research Laboratory, Veterans Administration Hospital, 91343, Sepulveda, California, U.S.A.

    M. K. Menon, W. G. Clark & D. T. Masuoka

  2. Department of Biological Chemistry, University of California Center for Health Sciences, Los Angeles, California

    M. K. Menon, W. G. Clark & D. T. Masuoka

  3. Department of Medical Pharmacology and Therapeutics, College of Medicine, University of California, Irvine, California

    M. K. Menon, W. G. Clark & D. T. Masuoka

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  2. W. G. Clark
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Menon, M.K., Clark, W.G. & Masuoka, D.T. Possible involvement of the central dopaminergic system in the antireserpine effect of LSD. Psychopharmacology 52, 291–297 (1977). https://doi.org/10.1007/BF00426714

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