Abstract
The abstinence syndrome as precipitated in morphine-dependent rabbits by systemic administration of nalorphine was compared with the syndrome induced by application of nalorphine to the entire cerebroventricular system, or separated parts of it. Systemic nalorphine administration precipitated a syndrome characterized by motor excitation and other more peculiar symptoms. Small, intraventricularly-applied nalorphine dosages induced a similar behaviour pattern although some abdominal symptoms, present after systemic withdrawal, were lacking. Preconvulsive and convulsive symptoms, which are only abortive upon systemic withdrawal, became more prominent with higher doses of nalorphine, administered intraventricularly. A nearly identical behaviour pattern was observed when nalorphine was injected into the 4th ventricle. In contrast, the symptomatology was weak after injection of nalorphine into the anterior parts of the ventricular system when the antagonist could not reach the caudal parts (plug in the aquaeductus mesencephali). The convulsive symptoms after intraventricular withdrawal were accompanied by a large increase in body temperature. Bradycardia and irregularities in heart rhythm were also pronounced only after intraventricular withdrawal. These results indicate that, structures easily reached by nalorphine from the 4th ventricle and probably located in medullary and pontine parts of the brain stem, are important sites of action of morphine for the development of physical dependence on this drug.
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For a preliminary report see Proceedings of the XXV International Congress of Physiological Sciences, Munich 1971 p. 246.
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Herz, A., Teschemacher, H., Albus, K. et al. Morphine abstinence syndrome in rabbits precipitated by injection of morphine antagonists into the ventricular system and restricted parts of it. Psychopharmacologia 26, 219–235 (1972). https://doi.org/10.1007/BF00422698
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DOI: https://doi.org/10.1007/BF00422698