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The effect of the enantiomers of 3-PPP on conditioned avoidance responding in the rat

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Abstract

The effects of the enantiomers of 3-PPP on the maintenance of conditioned avoidance responding (CAR) were studied. The weak classical dopamine (DA) agonist (+)-3-PPP failed to interfere with CAR at any dose tested (0.8–13.6 mg/kg). Low doses of the drug produced sedation, while high doses produced behavioural stimulation. (-)-3-PPP, which acts as an antagonist on postsynaptic and as an agonist on autoreceptor DA sites, reduced avoidance with no effect on escape behaviour (6.8–13.6 mg/kg). However, this reduction of CAR occurred at doses much higher than those previously demonstrated to inhibit locomotor activity. This profile is discussed in relation to the behavioural effects of classical postsynaptic DA receptor antagonists.

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References

  • Arnt J (1982) Pharmacological specificity of conditioned avoidance response inhibition in rats: Inhibition by neuroleptics and correlation to dopamine receptor blockade. Acta Pharmacol Toxicol 51:321–329

    Google Scholar 

  • Bunney BS, Aghajanian GK (1975) Antipsychotic drugs and central dopaminergic neurons: A model for predicting therapeutic efficacy and incidence of extrapyramidal side effects. In: Sudilovsky A, Gershon S, Beer B (eds) Predicatability in psychopharmacology: Preclinical and clinical correlations. Raven, New York, pp 225–245

    Google Scholar 

  • Carlsson A (1983) Antipsychotic agents: Elucidation of their mode of action. In: Bruinvels J, Parnham MJ (eds) Discoveries in pharmacology, vol 1, Psycho- and neuro-pharmacology. Elsevier North Holland, Amsterdam (in press)

    Google Scholar 

  • Clark D, Carlsson A, Hjorth S, Svensson K, Engel J, Sanchez D (1982) Is 3-PPP a potential antispychotic agent? Evidence from animal behavioural studies. Eur J Pharmacol 83:131–134

    Google Scholar 

  • Clark D, Carlsson A, Hjorth S, Svensson K, Liljequist S, Engel J, Engberg G, Svensson TH, Wikström H (1983) Is 3-PPP a potential antipsychotic agent? In: Carlsson A, Nilsson JLG (eds) Dopamine Receptor Agonists, Acta Pharmaceutica Suecica Suppl I. Swedish Pharmaceutical Press, Stockholm, pp 145–153

    Google Scholar 

  • Courvoisier S, Ducrot R, Julou E (1957) Nouveaux aspects expérimentaux de l'activité centrale des dérivés de la phénothiazine. In: Garattini S, Ghetti V (eds) Psychotropic drugs. Elsevier North Holland, Amsterdam, pp 373–391

    Google Scholar 

  • Crow TJ, Deakin JFW, Longden A (1977) The nucleus accumbens—possible site of action of antipsychotic action of neuroleptic drugs. Psychol Med 7:213–221

    Google Scholar 

  • Fielding S, Lal H (1978) Behavioural actions of neuroleptics. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 10. Plenum, New York, pp 91–128

    Google Scholar 

  • Forsman A, Öhman R (1976) Pharmacokinetic studies on haloperidol in man. Curr Ther Res 20:319–336

    Google Scholar 

  • Herz A (1960) Drugs and the conditioned avoidance response. Int Rev Neurobiol 2:229–277

    Google Scholar 

  • Hjorth S, Carlsson A, Wikström H, Lindberg P, Sanchez D, Hacksell U, Arvidsson LE, Svensson U, Nilsson JLC (1981) 3-PPP, a new centrally acting DA-receptor agonist with selectivity for autoreceptors. Life Sci 28:1225–1238

    Google Scholar 

  • Hjorth S, Carlsson A, Clark D, Svensson K, Wikström H, Sanchez D, Lindberg P, Hacksell U, Arvidsson LE, Johansson A, Nilsson JLG (1983a) Pharmacological manipulation of central dopamine (DA) autoreceptors — biochemical and behavioural consequences. In: Carlsson A, Nilsson JLG (eds) Dopamine Receptor Agonists, Acta Pharmaceutica Suecica Suppl I. Swedish Pharmaceutical Press, Stockholm, pp 130–137

    Google Scholar 

  • Hjorth S, Carlsson A, Clark D, Svensson K, Wikström H, Sanchez D, Lindberg P, Hacksell U, Arvidsson LE, Johansson A, Nilsson JLG (1983b) Central dopamine receptor agonist and antagonist action of the enantiomers of 3-PPP. Psychopharmacology (in press)

  • Hornykiewicz O (1973) Dopamine in the basal ganglia. Its role and therapeutic implications. Br Med Bull 29:172–178

    Google Scholar 

  • Janssen PAJ, Niemegeers CJE, Schellekens KHL (1965) Is it possible to predict the clinical effects of neuroleptic drugs (major tranquillisers) from animal data. Arzneim Forsch 15:104–117

    Google Scholar 

  • Janssen PAJ, Van Bever WFM (1978) Structure-activity relationships of the butyrophenones and diphenylbutyl-piperidines. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 10, Neuroleptics and schizophrenia. Plenum, New York, pp 1–35

    Google Scholar 

  • Liebman JM, Fenton HM, Gerhardt S, Noreika L (1982) The dopamine autoreceptor agonists, TL-99 and 3-PPP attenuate self-stimulation but not avoidance responding in rats. Soc Neurosci Abstr 8:469

    Google Scholar 

  • Lyon M, Randrup A (1972) The dose response effect of amphetamine upon avoidance behaviour in the rat seen as a function of increasing stereotypy. Psychopharmacologia 23:334–347

    Google Scholar 

  • Martin GE, Haubrich DR, Williams M (1981) Pharmacological profiles of the putative autoreceptor agonists 3-PPP and TL-99. Eur J Pharmacol 76:15–23

    Google Scholar 

  • Matthyse S (1973) Antipsychotic drug actions: a clue to the neuropathology of schizophrenia. Fed Proc 32:200–205

    Google Scholar 

  • Niemegeers CJE, Verbruggen FJ, Janssen PAJ (1969) The influence of various neuroleptic drugs on shock avoidance responding in rats. Psychopharmacologia 16:161–174

    Google Scholar 

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Clark, D., Carlsson, A., Hjorth, S. et al. The effect of the enantiomers of 3-PPP on conditioned avoidance responding in the rat. Psychopharmacology 81, 14–17 (1983). https://doi.org/10.1007/BF00439266

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