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D2-like but not D1-like dopamine receptors are involved in the ventrolateral orbital cortex-induced antinociception: a GABAergic modulation mechanism.

Abstract：

:The ventrolateral orbital cortex (VLO) is part of an endogenous analgesic system consisting of an ascending pathway from the spinal cord to VLO via the thalamic nucleus submedius (Sm) and a descending pathway to the spinal cord relaying in the periaqueductal gray (PAG). This study examines whether activation of D(1)-like and D(2)-like dopamine receptors in VLO produces antinociception and whether GABAergic modulation is involved in the VLO, D(2)-like dopamine receptor activation-evoked antinociception. The radiant heat-evoked tail flick (TF) reflex was used as an index of nociceptive response in lightly anesthetized rats. Microinjection of the D(2)-like (D(2)/D(3)) dopamine receptor agonist quinpirole (0.1-2.0 microg), but not D(1)-like (D(1)/D(5)) receptor agonist SKF-38393 (1.0, 5.0 microg), into VLO produced dose-dependent antinociception which was antagonized by the D(2)-like (D(2)/D(3)) receptor antagonist raclopride (1.5 microg). We also found that VLO application of the GABA(A) receptor antagonist bicuculline or picrotoxin (100 ng) enhanced the quinpirole-induced inhibition of the TF reflex, whereas the GABA(A) receptor agonist muscimol (250 ng) or THIP (1.0 microg) significantly attenuated the quinpirole-induced inhibition. These results suggest that D(2)-like, but not D(1)-like, dopamine receptors are involved in VLO-induced antinociception and that GABAergic disinhibitory mechanisms participate in the D(2)-like receptor mediated effect. These findings provide support for the hypothesis that D(2)-like receptor activation may inhibit the inhibitory action of the GABAergic interneurons on the output neurons projecting to PAG leading to activation of the brainstem descending inhibitory system and depression of nociceptive inputs at the spinal dorsal horn.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Sheng HY,Qu CL,Huo FQ,Du JQ,Tang JS

doi

10.1016/j.expneurol.2008.09.018

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

128-34

issue

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(08)00375-0

journal_volume

215

pub_type

杂志文章

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D2-like but not D1-like dopamine receptors are involved in the ventrolateral orbital cortex-induced antinociception: a GABAergic modulation mechanism.