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
DOI: 10.1038/sj.npp.1300033
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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.
Author information:
(1)Lab de Neuropsychobiologie des Désadaptions, Université de Bordeaux II,
Bordeaux, France.
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.
DOI: 10.1038/sj.npp.1300033
PMID: 12589380 [Indexed for MEDLINE]