AMT catalepsy and hypokinesia: Interaction with morphine and cocaine
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Acute morphine induced a dose-dependent hypokinesia and rigidity, but only mild and non-dose-dependent catalepsy. AMT, injected 1/2 h after morphine, slightly potentiated catalepsy but not hypokinesia during 3 h after morphine; in contrast, rigidity was decreased. The behavioral changes induced by AMT were accelerated in onset and reached their usual development, although AMT toxicity and hypothermia were completely antagonized; thus, it would appear that AMT hypokinesia/catalepsy are not the consequence of toxicity. When morphine was injected 4 h after AMT, a mutual potentiation of the two drugs on hypokinesia and catalepsy was observed, although previous biochemical measurements had shown no effect of morphine on CA depletion under these conditions. Rigidity appeared to be antagonized.
After 17 days of repeated injections, morphine no longer elicited hypokinesia and catalepsy, but no cross-tolerance developed to the AMT behavioral changes. A similar lack of cross-tolerance to the effects of AMT or haloperidol was observed when morphine tolerance was induced by pellet implantation.
Catalepsy and hypokinesia developed in a much more pronounced way after two large i.p. doses than after small, multiple administrations of AMT; this difference was accompanied by a significantly lower concentration of brain DA, but not NA, in the former group.
The hyperthermic response observed after a 40 mg/kg s.c. injection of morphine was reversed to hypothermia when the same dose was given 4 or 10 h after CA synthesis inhibition.
Cocaine strongly antagonized AMT hypokinesia and catalepsy when given 8 1/2 h after AMT, and, although to a lesser extent, even when injected 12 1/2 h after AMT.
Key wordsAlpha-methyl-p-tyrosine Morphine Cocaine Catalepsy Hypokinesia Brain catecholamines Functional pool
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- Anton, A. H., Sayre, D. F.: A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines. J. Pharmacol. exp. Ther. 138, 360–375 (1962)Google Scholar
- Bevan, J. A., Verity, M. A.: Sympathetic nerve-free vascular muscle. J. Pharmacol. exp. Ther. 157, 117–124 (1967)Google Scholar
- BlÄsig, J., Herz, A., Reinhold, K., ZieglgÄnsberger, S.: Development of the physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia (Berl.) 33, 19–38 (1973)Google Scholar
- Costall, B., Naylor, R. J.: On catalepsy and catatonia and the predictability of the catalepsy test for neuroleptic activity. Psychopharmacologia (Berl.) 34, 233–241 (1974)Google Scholar
- Costall, B., Naylor, R. J.: Serotonergic involvement with the stereotypy/catalepsy induced by morphine-like agents in the rat. J. Pharm. Pharmacol. 27, 67–69 (1975)Google Scholar
- Ferguson, G. A.: Statistical analysis in psychology and education. New York-Toronto: McGraw-Hill 1966Google Scholar
- Fog, R.: On stereotypy and catalepsy: studies on the effect of amphetamines and neuroleptics in rats. Copenhagen: Munksgaard 1972Google Scholar
- Fujimoto, J. M.: Sites of action of narcotic analgesic drugs. The kidney. In: Narcotic drugs, biochemical pharmacology, D. H. Clouet, ed., p. 366. New York-London: Plenum Press 1971Google Scholar
- Gunne, L.-M.: The temperature response in rats during acute and chronic morphine administration. A study of morphine tolerance. Arch. int. Pharmacodyn. 129, 416–428 (1960)Google Scholar
- Herz, A.: über die Beeinflussung zentral dÄmpfender und erregender Morphinwirkungen durch Anticholinergica, Nicotinolytica und Antihistaminica an der Ratte. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 241, 236–253 (1961)Google Scholar
- Herz, A., BlÄsig, J., Papeschi, R.: Role of catecholaminergic mechanisms in the expression of the morphine abstinence syndrome in rats. Psychopharmacologia (Berl.) 39, 121–143 (1974)Google Scholar
- Janssen, P. A. J.: Extrapolation from animals to man. Catatonia: discussion. In: Animal behavior and drug action. CIBA Foundation Symposium, H. Steinberg, A. V. S. de Reuck, and J. Knight, ed. London: Churchill 1964Google Scholar
- Janssen, P. A. J., Niemegeers, C. J. E., Schellekens, K. J. L., Dresse, A., Lenaerts, F. M., Pinchard, A., Schaper, W. K. A., van Neuten, J. M., Verbruggen, F. J.: Pimozide, a chemically novel, highly potent and orally long acting neuroleptic drug. Part I. The comparative pharmacology of pimozide, haloperidol and chlorpromazine. Arzneimittel-Forsch. 18, 261–287 (1968)Google Scholar
- Kuschinsky, K., Hornykiewicz, O.: Morphine catalepsy in the rat: relation to striatal dopamine metabolism. Europ. J. Pharmacol. 19, 119–122 (1972)Google Scholar
- Laverty, R., Taylor, K. M.: The fluorometric assay of catecholamines and related compounds. Improvements and extensions to the hydroxyindole technique. Analyt. Biochem. 22, 269–279 (1968)Google Scholar
- Lotti V. J., Lomax, P., George, R.: N-allylnormorphine antagonism of the hypothermic effect of morphine in the rat following intracerebral and systemic administration. J. Pharmacol. exp. Ther. 150, 420–425 (1965)Google Scholar
- Maxwell, R. A., Wastila, W. B., Eckhardt, S. B.: Some factors determining the response of rabbit aortic strips to dl-norepinephrine-7-H3 hydrochloride and the influence of cocaine, guanethidine and methylphenidate on these factors. J. Pharmacol. exp. Ther. 151, 253–261 (1966)Google Scholar
- Mayer-Gross, W., Slater, E., Roth, M.: Clinical psychiatry. London: Cassell & Co. 1960Google Scholar
- Moore, K. E., Wright, P. F., Bert, K. K.: Toxicologic studies with alpha-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 155, 506–515 (1967)Google Scholar
- Morpurgo, C.: Effect of anti-Parkinson drugs on a phenothiazine-induced catatonic reaction. Arch. int. Pharmacodyn. 137, 84–90 (1962)Google Scholar
- Oka, T., Nozaki, M., Hosoya, E.: Effects of p-chlorophenylalanine and cholinergic antagonists on body temperature changes induced by the administration of morphine to nontolerant and morphine-tolerant rats. J. Pharmacol. exp. Ther. 180, 136–143 (1972)Google Scholar
- Papeschi, R.: Dopamine, extrapyramidal system and psychomotor function. Psychiat. Neurol. Neurochir. (Amst.) 75, 13–48 (1972)Google Scholar
- Papeschi, R.: Behavioral and biochemical interaction between AMT and (+)-amphetamine: relevance to the identification of the functional pool of brain catecholamines. Psychopharmacologia (Berl.) 45, 21–28 (1975)Google Scholar
- Papeschi, R., Randrup, A.: Catalepsy, sedation and hypothermia induced by alpha-methyl-p-tyrosine in the rat. An ideal tool for screening of drugs active on central catecholaminergic receptors. Pharmakopsychiat. 6, 137–157 (1973)Google Scholar
- Papeschi, R., Munkvad, I.: Relation of effects of neuroleptics in animals to pharmacological parkinsonism and antipsychotic action in man. In: Psychopharmacology, sexual disorders and drug abuse, T. A. Ban, J. R. Boissier, G. L. Gessa, H. Heimann, L. Hollister, H. E. Lehmann, I. Munkvad, H. Steinberg, F. Sulser, A. Sundwall, and O. Vinar, eds., pp. 415–429. Amsterdam: North-Holland Publ. Co. and Prague: Avicenum Press 1973Google Scholar
- Papeschi, R., Theiss, P., Herz, A.: The effect of morphine on catecholamine and serotonin turnover: acute morphine administration. Europ. J. Pharmacol. 34, 253–262 (1975)Google Scholar
- Reiffenstein, R. J.: Effects of cocaine on the rate of contraction to noradrenaline in the cat spleen strip: mode of action of cocaine. Brit. J. Pharmacol. 32, 591–597 (1968)Google Scholar
- Ross, S. B., Renyi, A. L.: Inhibition of the uptake of tritiated catecholamines by antidepressant and related agents. Europ. J. Pharmacol. 2, 181–186 (1967)Google Scholar
- Ross, S. B., Rényi, A. L.: Inhibition of the uptake of 3H-dopamine and 14C-5-hydroxytryptamine in mouse striatum slices. Acta pharmacol. (Kbh.) 36, 56–66 (1975)Google Scholar
- Theiss, P., Papeschi, R., Herz, A.: The effect of morphine on catecholamine and serotonin turnover: chronic morphine administration. Europ. J. Pharmacol. 34, 263–272 (1975)Google Scholar
- Wand, P., Kuschinsky, K., Sontag, K.-H.: Morphine-induced muscular rigidity in rats. Europ. J. Pharmacol. 24, 189–193 (1973)Google Scholar
- Zetler, G.: Pharmacological differentiation of “nicotinic” and “muscarinic” catalepsy. Neuropharmacology 10, 289–296 (1971)Google Scholar