Inhibition of 5-HT neurotransmission increases clonidine protective effects on naloxone-induced conditioned place aversion in morphine-dependent rats.
Neuropsychopharmacol. 2002-07-15; 28(2): 276-283
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1. Neuropsychopharmacology. 2003 Feb;28(2):276-83. Epub 2002 Jul 15.
Inhibition of 5-HT neurotransmission increases clonidine protective effects on
naloxone-induced conditioned place aversion in morphine-dependent rats.
Caillé S(1), Stinus L, Espejo EF, De Deurwaerdère P, Spampinato U, Koob GF.
(1)Lab de Neuropsychobiologie des Désadaptions, Université de Bordeaux II,
Previous pharmacological studies have implicated serotonergic brain systems in
opiate-withdrawal-precipitated conditioned place aversion. To assess this
hypothesis, we tested the effects of either (i). a near-total
5,7-dihydroxytryptamine-induced lesion (90% depletion) or (ii). an acute
serotonin (5-HT) inhibition induced by the specific stimulation of 5-HT1A
autoreceptors (8-OHDPAT 5-100 microg/kg), on naloxone-induced conditioned place
aversion in morphine-dependent rats. Morphine dependence was induced by the
implantation of morphine slow-release pellets. The protective properties of
clonidine (an alpha-2 adrenergic agonist classically given for opiate
detoxification) were also tested after inhibition of 5-HT transmission.
Serotonergic lesions in morphine-dependent rats failed to alter naloxone-induced
conditioned place aversion but increased the sensitivity to the protective
effects of clonidine. Acute neuropharmacological blockade of serotonin
transmission also potentiated the clonidine effects on naloxone-induced
conditioned place aversion. When combined with the 5-HT1A agonist 8-OHDPAT,
clonidine was also found to be more potent. Further understanding of this
serotonin/noradrenaline interaction might help devise new therapeutic treatments
for the acute opiate withdrawal syndrome.
PMID: 12589380 [Indexed for MEDLINE]