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Influence of 6-hydroxydopamine on the effect of morphine on the tail-flick latency

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Abstract

One week following the intraventricular administration on successive days of two doses of 6-hydroxydopamine (6-OHDA) (0.1–1 mg/kg) to rats, the norepinephrine (NE) and dopamine (DA) contents in the brain were markedly decreased. These treatments potentiated the effect of morphine on the tail-flick latency after intraperitoneal or intraventricular administration of morphine. The intraventricular administration of two doses of 6-OHDA (0.5 mg/ kg) did not change the morphine concentrations in brain or plasma, or the duration of pentobarbital anesthesia. After 6-OHDA (total=20 Μg) had been injected bilaterally into the medial hypothalamic areas at the level of the ventromedial or dorsomedial hypothalamic nuclei, or into the medial forebrain bundle, morphine analgesia was also potentiated and there was marked reduction of the hypothalamic NE levels. The administration of high doses (2 mg/kg) of 6-OHDA into the lateral ventricles decreased the enhanced morphine analgesia and markedly depleted the brain NE and dopamine concentrations. The administration bilaterally of 6-OHDA (total=20 Μg) into caudatus-putamen areas reduced morphine analgesia.

In conclusion, 6-OHDA induced depletion of NE content in the hypothalamus potentiates morphine analgesia, whereas depletion of DA in the caudate nucleus decreases morphine analgesia.

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  1. K. Nakamura

    Present address: Nippon Roche Research Center, 247, Kamakura, Japan

Authors and Affiliations

  1. Departments of Biochemistry and Drug Metabolism, Hoffmann-La Roche Inc., 07110, Nutley, New Jersey, USA

    K. Nakamura, R. Kuntzman, A. C. Maggio & A. H. Conney

  2. Department of Pharmacology, Hoffmann-La Roche Inc., 07110, Nutley, New Jersey, USA

    V. Augulis

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Nakamura, K., Kuntzman, R., Maggio, A.C. et al. Influence of 6-hydroxydopamine on the effect of morphine on the tail-flick latency. Psychopharmacologia 31, 177–189 (1973). https://doi.org/10.1007/BF00419817

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