Abstract
Rats were initially trained to discriminate LSD from saline in two-lever operant chambers by reinforcing responses only on one lever following intraperitoneal injections of 80 Μg/ kg of LSD and only on the other lever following saline injections. Choice responding during extinction periods (no water reinforcement for either response) indicated a high level of discriminability (95% correct) following either LSD or saline. A dose-response curve for LSD, obtained by tests for lever choice after injections of 10, 20, 30, 40, 50, and 60 Μg/kg, indicated that 10 Μg/kg produced only 30% responding on the LSD lever. This percentage was increased (to 83%) by reinforcing responding on the LSD lever following injections of 10 Μg/kg. Subsequent tests indicated that doses of 5.0 and 2.5 Μg/kg produced a majority of responses on the LSD lever. Since at these low doses LSD has few measurable biochemical or behavioral effects, we hypothesize that the discriminable cue of LSD is related to direct stimulation of central serotonergic receptors.
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References
Aghajanian, G. K., Foote, W. E., Sheard, M. H.: Lysergic acid diethylamide: sensitive neuronal units in the midbrain raphe. Science 161, 706–708 (1968)
Aghajanian, G. K., Foote, W. E., Sheard, M. H.: Action of psychotomimetic drugs on single midbrain raphe neurons. J. Pharmacol. exp. Ther. 171, 178–187 (1970)
Aghajanian, G. K., Haigler, H. J., Bloom, F. E.: Lysergic acid diethylamide and serotonin: Direct actions on serotonin-containing neurons. Life Sci. 11, 615–622 (1972)
Appel, J. B., Freedman, D. X.: Chemically-induced alterations in the behavioral effects of LSD-25. Biochem. Pharmacol. 13, 861–869 (1964)
Appel, J. B., Lovell, R. A., Freedman, D. X.: Alterations in the behavioral effects of LSD by pretreatment with p-chlorophenylalanine and alpha-methyl-p-tyrosine. Psychopharmacologia (Berl.) 18, 387–406 (1970)
Barry, H., III.: Classification of drugs according to their discriminable effects in rats. Fed. Proc. 33, 1814–1824 (1974)
Browne, R. G., Harris, R. T., Ho, B. T.: Stimulus properties of mescaline and N-methylated derivatives: Difference in peripheral and central administration. Psychopharmacologia (Berl.) 39, 43–56 (1974)
Cameron, O. G., Appel, J. B.: A behavioral and pharmacological analysis of some discriminable properties of d-LSD in rats. Psychopharmacologia (Berl.) 33, 117–134 (1973)
Freedman, D. X.: Effects of LSD-25 on brain serotonin. J. Pharmacol. exp. Ther. 134, 160–166 (1961)
Freedman, D. X., Boggan, W. O.: Brain serotonin metabolism after tolerance dosage of LSD. In: Advances in biochemical psychopharmacology, Vol. 10, E. Costa, G. L. Gessa, and M. Sandler, eds. New York: Raven Press 1974
Haigler, H. J., Aghajanian, G. K.: Lysergic acid diethylamide and serotonin: A comparison of effects on serotonergic neurons and neurons receiving a serotonergic input. J. Pharmacol. exp. Ther. 188, 688–699 (1974a)
Haigler, H. J., Aghajanian, G. K.: Peripheral serotonin antagonists: Failure to antagonize serotonin in brain areas receiving a prominent serotonergic input. J. Neural Trans. 35, 257–273 (1974b)
Harris, R. T., Balster, R. L.: An analysis of the function of drugs in the stimulus control of operant behavior. In: Stimulus properties of drugs. T. Thompson and R. Pickens, eds. New York: Appleton-Century-Crofts 1971
Hirschhorn, I. D., Rosecrans, J. A.: A comparison of the stimulus effects of morphine and lysergic acid diethylamide (LSD). Pharmacol. Biochem. Behav. 2, 361–366 (1974)
Hirschhorn, I. D., Winter, J. C.: Mescaline and lysergic acid diethylamide (LSD) as discriminative stimuli. Psychopharmacologia (Berl.) 22, 64–71 (1971)
Kuhn, D. M., Greenberg, I., Appel, J. B.: An analysis of some discriminative properties of d-amphetamine. Psychopharmacologia (Berl.) 39, 57–66 (1974)
Overton, D. A.: Discriminative control of behavior by drug states. In: Stimulus properties of drugs. T. Thompson and R. Pickens, eds. New York: Appleton-Century-Crofts 1971
Overton, D. A.: State-dependent learning produced by addicting drugs. In: Opiate addiction: Origins and treatment. S. Fisher and A. M. Freedman, eds. Washington: Winston and Sons 1973
Overton, D. A.: Experimental methods for the study of state-dependent learning. Fed. Proc. 33, 1800–1813 (1974)
Rosecrans, J. A., Goodloe, M. H., Bennett, G. J., Hirschhorn, I. D.: Morphine as a discriminative cue: Effects of amine depletors and naloxone. Europ. J. Pharmacol. 21, 252–256 (1973)
Schechter, M. D., Rosecrans, J. A.: Lysergic acid diethylamide (LSD) as a discriminative cue: Drugs with similar stimulus properties. Psychopharmacologia (Berl.) 26, 313–316 (1972)
Waters, W. H., Richards, D. W., III., Harris, R. T.: Discriminative control and generalization of the stimulus properties of d,l-amphetamine in the rat. In: Drug Addiction, Vol. I. J. M. Singh, L. Miller, and H. Lal, eds. Mt. Kisco, New York: Futura Publishing 1972
Winter, J. C.: A comparison of the stimulus properties of mescaline and 2,3,4-trimethoxyphenylethylamine. J. Pharmacol. exp. Ther. 185, 101–107 (1973)
Winter, J. C.: The effects of 3,4-dimethoxyphenylethylamine in rats trained with mescaline as a discriminative stimulus. J. Pharmacol. exp. Ther. 189, 741–747 (1974)
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Greenberg, I., Kuhn, D.M. & Appel, J.B. Behaviorally induced sensitivity to the discriminable properties of LSD. Psychopharmacologia 43, 229–232 (1975). https://doi.org/10.1007/BF00429255
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DOI: https://doi.org/10.1007/BF00429255