Search

The role of dopaminergic system in modulation of formalin-induced orofacial nociception has been established. The present study aims to investigate the role of dopaminergic receptors in the nucleus accumbens (NAc) in modulation of nociceptive responses induced by formalin injection in the orofacial region. One hundred and six male Wistar rats were unilaterally implanted with two cannulae into the lateral hypothalamus (LH) and NAc. Intra-LH microinjection of carbachol, a cholinergic receptor agonist, was done 5min after intra-accumbal administration of different doses of SCH23390 (D1-like receptor antagonist) or sulpiride (D2-like receptor antagonist). After 5min, 50μl of 1% formalin was subcutaneously injected into the upper lip for inducing the orofacial pain. Carbachol alone dose-dependently reduced both phases of the formalin-induced orofacial pain. Intra-accumbal administration of SCH23390 (0.25, 1 and 4μg/0.5μl saline) or sulpiride (0.25, 1 and 4μg/0.5μl DMSO) before LH stimulation by carbachol (250nM/0.5μl saline) antagonized the antinociceptive responses during both phases of orofacial formalin test. The effects of D1- and D2-like receptor antagonism on the LH stimulation-induced antinociception were almost similar during the early phase. However, compared to D1-like receptor antagonism, D2-like receptor antagonism was a little more effective but not significant, at blocking the LH stimulation-induced antinociception during the late phase of formalin test. The findings revealed that there is a direct or indirect neural pathway from the LH to the NAc which is at least partially contributed to the modulation of formalin-induced orofacial nociception through recruitment of both dopaminergic receptors in this region., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The orexins (hypocretins) are lateral hypothalamic (LH) neuropeptides that have been implicated in a variety of behaviors ranging from feeding to sleep and arousal. Evidence from animal models suggests a role for orexins in reward processing and drug addiction. In the present study, we investigated the direct effect of an orexin antagonist in the ventral tegmental area (VTA) on acquisition and expression of morphine conditioned place preference (CPP) induced by concurrent stimulation of the LH. Eighty-one adult male Wistar rats weighing 220-280 g were unilaterally implanted by two separate cannulae into the LH and VTA. The CPP paradigm was done; conditioning score and locomotor activity were recorded by Ethovision software. The animals received SB334867 as a selective orexin-1 receptor antagonist (0.1, 1 and 10 nmol/0.3 μl DMSO) in the VTA, just 5 min prior to intra-LH administration of ineffective dose of carbachol as a cholinergic agonist (62.5 nmol/0.5 μl saline) that stimulates orexin neurons in the LH and ineffective dose of morphine (1 mg/kg, subcutaneously) concurrently during conditioning phase (acquisition experiments) or post-conditioning phase (expression experiments). Data showed that the blockade of orexin-1 receptors in the VTA could inhibit the acquisition (development) but not expression of LH stimulation-induced morphine CPP in the rats. Our findings suggest that the orexinergic projections from the LH to the VTA are involved in the development of the LH stimulation-induced potentiation of morphine rewarding properties and orexin-1 receptors in the VTA have a substantial role in this phenomenon., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Orexinergic projections from the lateral hypothalamus (LH) have an important role in acquisition of morphine conditioned place preference (CPP). However, little is known about the functional interaction between orexinergic and opioidergic systems in the reward circuitry in the rats. In the present study, we investigated the effects of different doses of carbachol, for chemical stimulation of LH, on rewarding properties of morphine in the rats. 132 adult male albino Wistar rats weighing 220-320 g were unilaterally implanted by a cannula into the LH. The CPP paradigm was done; conditioning score and locomotor activity were recorded by Ethovision software. In this paradigm, we used different doses of carbachol (31.25, 62.5, 125 and 250 nmol/0.5 μl saline), as a cholinergic agonist, in the LH. In the next set of experiment, we concurrently administered the ineffective doses of carbachol (31.25 and 62.5 nmol) and morphine (1mg/kg; a dose that produced no appreciable effect when given alone) during 3-day conditioning (Acquisition) and post-conditioning (Expression) phases. Our results showed that unilateral intra-LH administration of both ineffective doses of carbachol during conditioning phase significantly (P<0.01) potentiated the development of CPP by morphine (1mg/kg). However, in the expression experiments, only dose of 62.5 nmol/rat carbachol could induce morphine-CPP (P<0.05). Our findings suggest that a chemical stimulation of LH in sub-threshold condition could potentiate rewarding properties of morphine through mechanisms involved in alteration of dopamine release or morphine sensitization at the level of nucleus accumbens and/or ventral tegmental area by orexin receptors in the rats., (Copyright © 2013 Elsevier Inc. All rights reserved.)