Effect of orexin receptor-1 agonist and antagonist microinjection into the ventral tegmental area on morphine withdrawal syndrome

Several Studies have identified that the mesocorticolimbic dopaminergic pathway consisting of the ventral tegmental area (VTA) and the nucleus accumbens (NAc) plays an important role in morphine dependence and withdrawal signs. Orexin projection and its receptors have been found in the brain regions including VTA that involved in the expression of morphine withdrawal signs. The aim of this study was to evaluate the effects of orexin receptor-1 (OX1R) agonist and antagonist microinjection into the VTA on withdrawal signs in morphine dependent rats. This experimental study was carried out on 24 male Wistar rats (weighing 250-300 g) in 2012 that were divided in 4 groups. They were rendered morphine dependent by subcutaneous injection of morphine sulfate at intervals of 12 h for 10 days. On day 11، intra-VTA microinjection of orexin receptor-1 agonist (orexin-A) and antagonist (SB-334867) was performed (2h after last morphine injection and before naloxan injection) and naloxone precipitated withdrawal sings were evaluated for 30 min. In the vehicle group، normal salin was microinjected into the VTA. Data were analyzed using t-test and ANOVA. Intra-VTA SB-334867 microinjection significantly decreased the jumping sign (P< 0. 01). Orexin-A microinjection significantly increased the wet-dog shakes sign (P< 0. 05). With regard to the results، OX1R in the VTA has a little effect on expression of withdrawal signs in morphine dependent rats.