Involvement of orexin-2 receptors in the ventral tegmental area andnucleus accumbens in the antinociception induced by the lateralhypothalamus stimulation in rats

Orexin, which is mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), playsan important role in pain modulation. Both kinds of orexin-1 (Ox1) and orexin-2 (Ox2) receptors havebeen found at high density in the ventral tegmental area (VTA) and nucleus accumbens (NAc). However,the quantity of Ox1 receptors in the VTA is more than that in the NAc. Additionally, it seems that thefunctional interaction between the LH, VTA and NAc implicates pain processing and modulation. In thisstudy, we tried to examine the involvement of Ox2 receptors in the NAc and VTA using tail-flick test asan animal model of acute pain following microinjection of effective dose of carbachol (125 nmol/0.5 �lsaline) into the LH. In this set of experiments, different doses of TCS OX2 29 as an Ox2 receptor antagonistwere microinjected into the VTA (1, 7 and 20 nmol/0.3 �l DMSO) and the NAc (2, 10, 20 and 40 nmol/0.5 �lDMSO) 5 min prior to carbachol administration. Administration of TCS OX2 29 into the VTA and NAc dose-dependently blocked intra-LH carbachol-induced antinociception. However, the inhibitory effect of TCSOX2 29 as an Ox2 receptor antagonist was more potent in the VTA than that in the NAc. It seems that VTAorexinergic receptors are more effective on LH stimulation-induced antinociception and the modulationof pain descending inhibitory system originated from the LH than those of the same receptors in thenucleus accumbens in rats