Lateral hypothalamus chemical stimulation-induced antinociception was attenuated by injection of dopamine D1 and D2 receptor antagonists in the ventral tegmental area

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. 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. 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. 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.