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The influence of morphine dependence on some specific effects mediated by monoaminergic and GABAergic systems

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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functions were then monitored during withdrawal from the morphine treatment in comparison with controls withdrawn from saline at 40, 64, 112, and 184 h after the last injection.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due to dopaminergic stimulation by apomorphine (1.5 and 2 mg/kg SC) was significantly potentiated in the rats withdrawn from morphine.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(150 mg/kg SC) preceded by the decarboxylase inhibitor benserazide (50 mg/kg IP) was similar in animals withdrawn from either morphine or saline.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or D,L-4-amino-hex-5-enoic acid (RMI 71754) (γ-vinyl GABA) (800 mg/kg IP) did not differ significantly between morphine-withdrawn and saline-treated rats.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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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).

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Key words

  • Morphine withdrawal
  • Neurotransmitter sensitivity
  • GABA
  • Serotonin
  • Acetylcholine
  • Dopamine