role of orexin-1 receptor within the ventral tegmental area in mediating stress- and morphine priming-induced reinstatement of conditioned place preference in rats

Introduction: orexin-containing neurons exist in the lateral hypothalamic region, sending their projections toward mesolimbic regions such as the ventral tegmental area (vta). methods: in the current study, a reinstatement model is used to examine the effects of intra-vta administration of sb334867 as an orexin-1 receptor (ox1r) antagonist on drug priming- and forced swim stress (fss)-induced reinstatement of morphine. eighty-eight male adult albino wistar rats, weighing 200-280 g, were bilaterally implanted by cannulas into the vta. we induced the conditioned place preference (cpp) by subcutaneous (sc) injection of morphine (5 mg/kg) daily in three days. then, the cpp score was calculated. after a 24-h “off” period following achievement of extinction criterion, the rats were tested for drug priminginduced reinstatement by a priming dose of morphine (1 mg/kg, sc) and for fss-induced reinstatement 10 min after fss. in the next experiments, the animals received different doses of intra-vta administration of sb334867 (0.3, 3, and 1 nm/0.3 μl 12% dmso per side) and bilaterally were subsequently tested for fss- and morphine priming-induced reinstatement. results: our findings indicated that the fss could induce the reinstatement of seeking behaviors. furthermore, intra-vta administration of ox1r antagonists suppressed fss- and drug priming-induced reinstatement dose-dependently. conclusion: it is concluded that fss and drug priming-induced reinstatement might be mediated, at least in part, by stimulation of orexin receptors in the vta.