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Introduction: Stimulation or inactivation of the lateral hypothalamus (LH) produces antinociception. Studies showed a role for the ventral tegmental area (VTA) in the antinociception induced by LH chemical stimulation through the orexinergic receptors. In this study, we assessed the role of intra-VTA dopamine D1 and D2 receptors in antinociceptive effects of cholinergic agonist, carbachol, microinjected into the LH in the tail-flick test. Methods: Rats were unilaterally implanted with two separate cannulae into the VTA and LH. Intra-VTA infusions of selective D1 receptor antagonist SCH-23390 (0.125, 0.25, 1 and 4 μg/0.3 μl saline) and selective D2 receptor antagonist sulpiride (0.125, 0.25, 1 and 4 μg/0.3 μl DMSO) 2 min before microinjection of carbachol (125 nmol/rat effective dose) into the LH was done. The antinociceptive effects of different doses of these antagonists were measured using a tail-flick analgesiometer, and represented as maximal possible effect (%MPE) at 5, 15, 30, 45 and 60 min after administration. Results: The results showed that intra-VTA administration of D1 and D2 dopamine receptors antagonists could significantly prevent the development of LH stimulation-induced antinociception. Administration of maximum doses of SCH-23390 and Sulpiride (4 μg) didn’t affect the nociceptive behaviors in acute model of pain. Conclusion: Thus dopamine receptors in the VTA play a modulating role in carbachol-induced analgesia within the LH, in acute model of pain. It is supposed that there is an interaction between VTA dopaminergic and orexinergic systems in pain modulation.

Keywords: Pain, Lateral Hypothalamus, Ventral tegmental area, Dopamine D1 receptors, Dopamine D2 receptors

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