Skip to main content
SpringerLink
Log in

Effects of chlorpromazine and three metabolites on behavioral responses in rats

  • Published:
Psychopharmacologia Aims and scope Submit manuscript

Abstract

Effects of chlorpromazine (CPZ) and three metabolites (3,7-dihydroxy-CPZ; 7,8-dihydroxy-CPZ; 7-hydroxy-CPZ) on behavioral performance of rats were tested by three methods: (a) continuous nondiscriminative lever-pressing shock-avoidance response without a warning signal; (b) discriminative pole-climbing shock avoidance and escape; (c) discriminative control of behavior by drug states. Both types of avoidance were much more impaired by CPZ than by the metabolites. The metabolite producing the most consistent impairment was 7-hydroxy-CPZ and the least consistent was 7,8-dihydroxy-CPZ. In the test for discriminative control of behavior by drug states, the 7-hydroxy-CPZ was the only metabolite which evoked the CPZ stimulus characteristics whereas the 7,8-dihydroxy-CPZ produced a generalized depressant effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aceto, M. D. G., Kinnard, W. J., Buckley, J. P.: Effect of compounds on blood pressure and behavioral responses of rats chronically subjected to an avoidance-escape situation. Arch. int. Pharmacodyn. 144, 214–225 (1963)

    Google Scholar 

  • Barry, H., III, Buckley, J. P.: Drug effects on animal performance and the stress syndrome. J. pharm. Sci. 55, 1159–1183 (1966)

    Google Scholar 

  • Barry, H., III, Krimmer, E. C.: Pentobarbital effects perceived by rats as resembling several other depressants but not alcohol. Proc., 80th Annual Convention, Amer. Psychol. Assoc. 7, 849–850 (1972)

    Google Scholar 

  • Barry, H., III, Kubena, R. K.: Discriminative stimulus characteristics of alcohol, marihuana and atropine. In: Drug addiction: Experimental pharmacology, J. M. Singh, L. H. Miller, and H. Lal (Ed.), pp. 3–16. Mount Kisco, N.Y.: Futura Publishing Co. 1972

    Google Scholar 

  • Buckley, J. P., Solaro, R. J., Barry, H., III: Effects of phenformin HCl on rats subjected to simulated high altitude. J. pharm. Sci. 58, 348–351 (1969)

    Google Scholar 

  • Buckley, J. P., Steenberg, M. L., Barry, H., III, Manian, A. A.: Pharmacology of mono- and disubstituted chlorpromazine metabolites. J. pharm. Sci. 62, 715–722 (1973)

    Google Scholar 

  • 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.), pp. 111–132. New York: Appleton-Century-Crofts 1971

    Google Scholar 

  • Kubena, R. K., Barry, H., III: Two procedures for training differential responses in alcohol and nondrug conditions. J. pharm. Sci. 58, 99–101 (1968a)

    Google Scholar 

  • Kubena, R. K., Barry, H., III: Generalization by rats of alcohol and atropine stimulus characteristics to other drugs. Psychopharmacologia (Berl.) 15, 196–206 (1968b)

    Google Scholar 

  • Manian, A. A., Efron, D. H., Harris, S. R.: Appearance of monohxydroxylated chlorpromazine metabolites in the central nervous system. Life Sci. Part I, 10, 679–684 (1971)

    Google Scholar 

  • NybÄck, H., Sedvall, G.: Effect of chlorpromazine and some of its metabolites on synthesis and turnover of catecholamines formed from 14C-tyrosine in mouse brain. Psychopharmacologia (Berl.) 26, 155–160 (1972)

    Google Scholar 

  • Overton, D. A.: State-dependent learning produced by depressant and atropine-like drugs. Psychopharmacologia (Berl.) 10, 6–31 (1966)

    Google Scholar 

  • Stewart, J.: Differential responses based on the physiological consequences of pharmacological agents. Psychopharmacologia (Berl.) 3, 132–138 (1962)

    Google Scholar 

  • Watzman, N., Manian, A. A., Barry, H., III, Buckley, J. P.: Comparative effects of chlorpromazine hydrochloride and quaternary chlorpromazine hydrochloride on the central nervous systems of rats and mice. J. pharm. Sci. 57, 2089–2093 (1968)

    Google Scholar 

Download references

Author information

Author notes

  1. Marie L. Steenberg & Joseph P. Buckley

    Present address: University of Houston College of Pharmacy, Cullen Boulevard, 77004, Houston, TX

Authors and Affiliations

  1. Department of Pharmacology, University of Pittsburgh School of Pharmacy, 15261, Pittsburgh, PA

    Herbert Barry III, Marie L. Steenberg, Albert A. Manian & Joseph P. Buckley

Authors
  1. Herbert Barry III
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marie L. Steenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Albert A. Manian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joseph P. Buckley
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by PHS Research Grants MH-13595 and MH-19719 from the NIMH. The first author (H. B.) was supported by PHS Research Scientist Development Award K2-MH-5921 from the NIMH.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barry, H., Steenberg, M.L., Manian, A.A. et al. Effects of chlorpromazine and three metabolites on behavioral responses in rats. Psychopharmacologia 34, 351–360 (1974). https://doi.org/10.1007/BF00422558

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00422558

Key words

Search

Navigation