Physical dependence in rats was attained by increasing doses of morphine twice daily for 14 days. The effects of drugs modifying neurotransmitter functions were then monitored during withdrawal from the morphine treatment in comparison with controls withdrawn from saline at 40, 64, 112, and 184 h after the last injection. The stereotypy due to dopaminergic stimulation by apomorphine (1.5 and 2 mg/kg SC) was significantly potentiated in the rats withdrawn from morphine. Characteristic wet-dog shake behavior induced by elevating brain levels of serotonin (5-HT) with 5-hydroxy-DL-tryptophan (150 mg/kg SC) preceded by the decarboxylase inhibitor benserazide (50 mg/kg IP) was similar in animals withdrawn from either morphine or saline. The hypothermia and the general behavior following elevation of brain GABA levels with the GABA transaminase inhibitors D,L-4-amino-hex-5-ynoic acid (RMI 71645) (γ-acetylenic GABA) (100 mg/kg IP) or D,L-4-amino-hex-5-enoic acid (RMI 71754) (γ-vinyl GABA) (800 mg/kg IP) did not differ significantly between morphine-withdrawn and saline-treated rats. The central cholinergically mediated hypothermia and tremor induced by tremorine (15 mg/kg IP) was similar in both groups, but the peripheral chromodacryorrhea was blocked during morphine withdrawal. It is thus concluded that during morphine withdrawal in the rat under these conditions, the behavior mediated by dopaminergic system shows enhancement, but effects dependent upon central 5-HT, GABA, and cholinergic systems are not affected.
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Bedard, P., Pycock, C. J.: “Wet-dog” shake behavior in the rat: A possible quantitative model of central 5-hydroxytryptamine activity. Neuropharmacology 16, 663–670 (1977)
Breuker, E., Dingledine, R., Iversen, L. L.: Evidence for naloxone and opiates as GABA antagonists. Br. J. Pharmacol. 58, 458P (1976)
Buckett, W. R.: A new test for morphine-like physical dependence (addiction liability) in rats. Psychopharmacologia 6, 410–416 (1964)
Buckett, W. R.: Withdrawal from morphine dependence leads to selective sensitivity to neurotransmitters in the central nervous system. Vienna: Eleventh Congress, Collegium Internationale Neuropsychopharmacologicum (Abstracts), p. 434 (1978)
Carlson, K. R., Almási, J.: Behavioural supersensitivity to apomorphine following chronic narcotic treatment in the guinea pig. Psychopharmacology 57, 273–277 (1978)
Cheney, D. L., Trabucchi, M., Racagni, G., Wang, C., Costa, E.: Effects of acute and chronic morphine on regional rat brain acetylcholine turnover rate. Life Sci. 15, 1977–1990 (1973)
Clouet, D. G., Neidle, A.: The effect of morphine on the transport and metabolism of intracisternally injected leucine in the rat. J. Neurochem. 17, 1069–1074 (1970)
Domino, E. F., Wilson, A.: Effects of narcotic analgesic agonists and antagonists on rat brain acetylcholine. J. Pharmacol. Exp. Ther. 184, 18–32 (1973)
Gibson, A., Pollock, D.: The involvement of corticosteroids in the supersensitivity produced in the rat anococcygeus muscle by morphine withdrawal, thyroidectomy or a single dose of reserpine. J. Pharmacol. Exp. Ther. 192, 390–398 (1975)
Glick, S. D., Cox, R. D.: Changes in sensitivity to operant effects of dopaminergic and cholinergic agents following morphine withdrawal in rats. Eur. J. Pharmacol. 42, 303–306 (1977)
Ho, I. K., Loh, H. H., Way, E. L.: Effect of GABA on morphine analgesia, tolerance and physical dependence. Fed. Proc. 32, 758 (1973)
Ho, I. K., Loh, H. H., Way, E. L.: Pharmacological manipulation of gamma-aminobutyric acid in morphine analgesia, tolerance and physical dependence. Life Sci. 18, 1111–1124 (1976)
Hong, E., Sancilio, L. F., Vargas, R., Pardo, E. G.: Similarities between the pharmacological actions of quipazine and serotonin. Eur. J. Pharmacol. 6, 274–280 (1969)
Iversen, S. D., Joyce, E. M.: Effect in the rat of chronic morphine treatment on the behavioural response to apomorphine. Br. J. Pharmacol. 62, 390–391 (1978)
Jung, M., Metcalf, B. W.: Catalytic inhibition of γ-aminobutyric acid-ketoglutarate transaminase of bacterial origin by 4-aminohex-5-ynoic acid, a substrate analog. Biochem. Biophys. Res. Commun. 67, 301–306 (1975)
Kuschinsky, K.: Does chronic morphine treatment induce a supersensitivity of dopamine receptors in rat brain? Psychopharmacologia 42, 225–229 (1975)
Lin, S. C., Sutherland, V. C., Way, E. L.: Brain amino acids in morphine-tolerant and non-tolerant rats. Proc. West. Pharmacol. Soc. 16, 8–13 (1973)
Moroni, F., Cheney, D. L., Peralta, E., Costa, E.: Opiate receptor agonists as modulators of GABA turnover in nucleus caudatus, globus pallidus and substantia nigra of the rat. J. Pharmacol. Exp. Ther. 207, 870–877 (1978)
Schechter, P. J., Tranier, Y.: Effect of GABA-T inhibition on rectal temperature in mice. Pharmacol. Biochem. Behav. 6, 667–669 (1977)
Scheel-Krüger, J., Golembiowska, K., Mogilnicka, E.: Evidence for increased apomorphine-sensitive dopaminergic effects after acute treatment with morphine. Psychopharmacology 53, 55–63 (1977)
Schulz, R., Goldstein, A.: Morphine tolerance and supersensitivity to serotonin in the myenteric plexus of guinea pig. Nature 244, 168–170 (1973)
Schulz, R., Herz, A.: Aspects of opiate dependence in the myenteric plexus of the guinea pig. Life Sci. 19, 1117–1128 (1976)
Schulz, R., Herz, A.: Naloxone-precipitated withdrawal reveals sensitization to neurotransmitters in morphine tolerant/dependent rats. Naunyn Schmiedebergs Arch. Pharmacol. 299, 95–99 (1977)
Smee, M. L., Overstreet, D. H.: Alterations in the effects of dopamine agonists and antagonists on general activity in rats following chronic morphine treatment. Psychopharmacology 49, 125–130 (1976)
Tarsy, D., Baldessarini, R. J.: Behavioral supersensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic function of catecholamines. Neuropharmacology 13, 927–940 (1974)
Volicer, L., Puri, S. K., Choma, P.: Cyclic GMP and GABA levels in rat striatum and cerebellum during morphine withdrawal: Effect of apomorphine. Neuropharmacology 16, 791–794 (1977)
A preliminary account of these findings was communicated to the Eleventh C.I.N.P. Meeting (Buckett, 1978)
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Buckett, W.R. The influence of morphine dependence on some specific effects mediated by monoaminergic and GABAergic systems. Psychopharmacology 66, 233–238 (1979). https://doi.org/10.1007/BF00428311
- Morphine withdrawal
- Neurotransmitter sensitivity