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Role of catecholaminergic mechanisms in the expression of the morphine abstinence syndrome in rats

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Abstract

The effect of various drugs affecting catecholaminergic mechanisms on the precipitated morphine withdrawal syndrome was studied in rats which had developed a medium degree of dependence. Administration of low doses of d-amphetamine, cocaine, and L-Dopa shortly before precipitating withdrawal by levallorphan induced a dose-dependent increase of “dominant” withdrawal signs such as jumping and a decrease of “recessive” signs such as wet dog shaking; signs such as diarrhea and ptosis decreased, whereas rhinorrhea, salivation and lacrimation increased. A qualitatively very similar change in withdrawal signs occurred when withdrawal was precipitated in extremely highly dependent rats and/or increasing doses of the antagonist were administered. Therefore, the effects of the above drugs are interpreted as potentiation of withdrawal. Pretreatment with higher doses of the same drugs provoked strong stereotyped behaviour which obviously suppressed the occurrence of other motor signs.

Activation of noradrenergic or dopaminergic mechanisms with desipramine or apomorphine induced an increase in the intensity of withdrawal, which was, however, much more pronounced after the former than the latter drug. When catecholamines (CA) were previously depleted by alpha-methyl-para-tyrosine (AMT), apomorphine lost a great part of its effectiveness. Blockade of CA synthesis by AMT alone resulted in decreased jumping while at the same time writhing largely increased, thus, inducing a profile of signs characteristic for a weak withdrawal. Selective inhibition of noradrenaline synthesis by FLA-63 resulted in a reduction in withdrawal intensity. Ro 4-4602 + L-Dopa, given after AMT, antagonized and reversed the reduction of withdrawal, but this effect was not so pronounced when by additional pretreatment with FLA-63 NA levels remained low. It is concluded that of both brain CA especially noradrenaline is involved in the manifestation of the morphine withdrawal syndrome.

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Authors and Affiliations

  1. Department of Neuropharmacology, Max-Planck-Institut für Psychiatrie, München, Germany

    A. Herz, J. BlÄsig & R. Paeschi

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  1. A. Herz
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  2. J. BlÄsig
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  3. R. Paeschi
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Herz, A., BlÄsig, J. & Paeschi, R. Role of catecholaminergic mechanisms in the expression of the morphine abstinence syndrome in rats. Psychopharmacologia 39, 121–143 (1974). https://doi.org/10.1007/BF00440843

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  • DOI: https://doi.org/10.1007/BF00440843

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