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Effects of acute selective 5-HT1, 5-HT2, 5-HT3 receptor andα 2 adrenoceptor blockade on naloxone-induced antinociception

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Abstract

Several studies have demonstrated a paradoxical form of antinociception induced by the repeated administration of opioid antagonists accompanied by exposure to a painful stimulus. The underlying mechanism of this naloxone-induced antinociception (NIA) is still unknown, but the results of several studies suggest that it is a non-opioid response. This study was designed to investigate serotonergic and noradrenergic involvement in NIA. Rats were treated daily with systemic injections of 5 mg/kg naloxone, followed by a 45-s hot plate test of nociception (temperature=51.5 ± 0.5°C). After rats reached plateau levels of NIA, they received a test trial in which they were treated with various doses of different selective 5-HT or α2 adrenoceptor antagonists in addition to naloxone before the hot plate test. Rats treated with 0.16, 0.32 and 0.63 mg/kg pirenperone or 2.5 mg/kg ritanserin showed significant reductions in paw lick latency with respect to rats treated with vehicle. In addition, high doses of yohimbine (7.5–10 mg/kg) also effectively reversed NIA. In contrast, NIA was not affected by acute blockade of 5-HT1 or 5-HT3 receptors by methiothepin or MDL 72222, respectively, or by the α2 adrenoceptor blocker idazoxan. None of the 5-HT or α2 adrenoceptor antagonists had any effect on the paw lick latencies of saline-treated rats. A possible role of 5-HT2 receptors in the antinociception induced by opioid receptor blockade is discussed.

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Authors and Affiliations

  1. Addiction Research Foundation, 33 Russell Street, M5S 2S1, Toronto, Ontario, Canada

    M. J. Katharine Walker, Constantine X. Poulos & A. D. Le

  2. Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada

    M. J. Katharine Walker

  3. Department of Psychology, University of Toronto, Toronto, Ontario, Canada

    Constantine X. Poulos

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  1. M. J. Katharine Walker
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  2. Constantine X. Poulos
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  3. A. D. Le
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Katharine Walker, M.J., Poulos, C.X. & Le, A.D. Effects of acute selective 5-HT1, 5-HT2, 5-HT3 receptor andα 2 adrenoceptor blockade on naloxone-induced antinociception. Psychopharmacology 113, 527–533 (1994). https://doi.org/10.1007/BF02245234

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