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
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
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)
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
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
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
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
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
Forsman A, Öhman R (1976) Pharmacokinetic studies on haloperidol in man. Curr Ther Res 20:319–336
Herz A (1960) Drugs and the conditioned avoidance response. Int Rev Neurobiol 2:229–277
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
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
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
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
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
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
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
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
Matthyse S (1973) Antipsychotic drug actions: a clue to the neuropathology of schizophrenia. Fed Proc 32:200–205
Niemegeers CJE, Verbruggen FJ, Janssen PAJ (1969) The influence of various neuroleptic drugs on shock avoidance responding in rats. Psychopharmacologia 16:161–174
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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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DOI: https://doi.org/10.1007/BF00439266