Cyclo-oxygenase-inhibitors increase morphine effects on mesolimbic dopamine neurons.

Abstract:

:The effect of cyclo-oxygenase inhibitors, indomethacin and nimesulide, on the action of i.v. morphine on dopamine neurons projecting to the nucleus Accumbens was studied using standard extracellular recording techniques coupled with antidromic identification in unanesthetized rats. The i.v. administration of either nimesulide (3 mg/kg) or indomethacin (3.5 mg/kg) per se did not affect the firing rate of mesolimbic dopamine cells. In contrast, the subsequent administration of morphine (0.25-2 mg/kg i.v.) potently increased the firing rate of mesolimbic dopamine neurons in cyclo-oxygenase inhibitor-pretreated rats as compared with saline-pretreated rats. The maximal enhancement of basal firing rate at the highest dose of morphine tested was 92%, 80% and 47%, for nimesulide-, indomethacin-, and saline-treated rats, respectively. Our results indicate that the effect of morphine on mesolimbic dopamine cells is potentiated by blocking cyclo-oxygenase activity and suggest that the modulation of cyclo-oxygenase pathway in dopamine cells might be involved in the cellular mechanisms of the rewarding actions of morphine.

journal_name

Eur J Pharmacol

authors

Melis M,Diana M,Gessa GL

doi

10.1016/s0014-2999(99)00799-2

keywords:

subject

Has Abstract

pub_date

2000-01-03 00:00:00

pages

R1-3

issue

1

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(99)00799-2

journal_volume

387

pub_type

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