Laleh Rezaee - Academia.edu (original) (raw)

Papers by Laleh Rezaee

Neuroscience Letters, Sep 1, 2018

Amitriptyline induced no antinociceptive effect in phase I of the formalin test in morphinedepend... more Amitriptyline induced no antinociceptive effect in phase I of the formalin test in morphinedependent and morphine-naïve rats.  In the interphase of the formalin test, amitriptyline induced pain suppression.  In phase II of the formalin test, amitriptyline induced hypoalgesic effect on pain-related behaviors in morphine-naïve rats.  In phase II of the formalin test, amitriptyline produced hyperalgesia at lower doses and hypoalgesia at higher doses in morphine-dependent rats.

Behavioral Neuroscience, Dec 1, 2019

Addiction to opioids is an important global problem. Published research has indicated the powerfu... more Addiction to opioids is an important global problem. Published research has indicated the powerful rewarding effects of drug use, which in the case of opiates like morphine may lead to drug addiction and maladaptive decision making with negative social consequences. In-depth comprehension of the role of responsible mechanisms in addiction can lead us to better and more effective treatments for drug dependence. Continuing previous work in our laboratory, in this study we aimed to investigate the role of dopamine D1- and D2-like receptors in the dentate gyrus (DG) on the reinstatement of drug-seeking behavior induced by the combination of forced swim stress and a subthreshold dose of morphine on extinguished morphine-conditioned place preference in rats. The rats were bilaterally implanted with 2 separate cannulas into the DG region. After the extinction phase of morphine-conditioned place preference, the animals received different doses (0.5, 2, and 4 μg per 0.5 μL vehicle/side) of SCH-23390 or sulpiride on the reinstatement day and were tested for the combination of forced swim stress and a subthreshold dose of morphine in discrete groups. Our findings indicated that D1- and D2-like receptor antagonists attenuated the reinstatement induced by the combination of FSS and the subthreshold dose of morphine. The reduction was more robust in groups of animals that received sulpiride as compared with SCH-23390. Our results showed a role for DG dopamine receptors in relapse to drugs of abuse, the activity of which may be induced by exposure to a stressor like forced swim stress. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Neuroscience Letters, Apr 1, 2021

The role of the ventral tegmental area (VTA) and the lateral hypothalamus (LH) in the modulation ... more The role of the ventral tegmental area (VTA) and the lateral hypothalamus (LH) in the modulation of formalin-induced nociception is well documented individually. The present study aimed to investigate the role of dopamine receptors of the VTA in the modulation of the LH stimulation-induced antinociception during both phases of the formalin test as an animal model of tonic pain. In this study, male Wistar rats were unilaterally implanted with two guide cannulae in the VTA and LH. In two separate groups, animals received different doses (0.25, 1, and 4 µg/rat) of D1- or D2-like dopamine receptor antagonists (SCH-23390 or Sulpiride, respectively) into the VTA before intra-LH injection of carbachol (22.83 ng/rat) following formalin injection (50 µl; s.c.) into their contralateral hind paws. The blockade of these two receptors reduced intra-LH carbachol-induced antinociception during both phases of the formalin test. This reduction during the late phase of the formalin test was more than that of the early phase. The results indicated that LH stimulation-induced antinociception was mediated by D1- and D2-like dopamine receptors in the VTA, and so, the neural pathway projecting from the LH to the VTA contributes to the modulation of formalin-induced nociception in the rats.

Neuropeptides, Jun 1, 2018

Effects of intrathecal administration of orexin-1 receptor antagonist on antinociceptive response... more Effects of intrathecal administration of orexin-1 receptor antagonist on antinociceptive responses induced by chemical stimulation of lateral hypothalamus in an animal model of tonic nociception. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Ynpep(2018),

Physiology & Behavior, Oct 1, 2019

The activation of glial cells affects the neuronal excitability in the spinal cord. Therefore, in... more The activation of glial cells affects the neuronal excitability in the spinal cord. Therefore, in this study, we tried to find out the modulatory role of spinal glial cells in the excitability of wide dynamic range (WDR) neurons, induction of the long-term potentiation (LTP) and development of neuropathic pain by L5 spinal nerve transection model in the rats. Forty-eight adult male Wistar rats were used to measure the paw withdrawal threshold to mechanical stimuli and also, to carry out the spinal extracellular single unit recording experiments. In these experiments, spinal nerve ligation (SNL) and a daily injection of propentofylline (1 mg/kg, ip) as a glial cell inhibitor agent, 1 h following nerve ligation during 7-day post-SNL period, were performed. Our findings showed that the mechanical allodynia, and synaptically-evoked firing were caused LTP in the Aδ-fiber, C-fiber and lesser in the Aβ-fiber after high frequency stimulation. Daily injection of propentofylline considerably decreased LTP induction in the Aδ-and C-fibers (P < .001). It was concluded that glial cell activation mediates LTP induction in the spinal cord following peripheral nerve injury. It seems that pain modulatory role of glial cells is partly parallel to changes in neural excitability of the WDR neurons in the dorsal horn of spinal cord.

Journal of Pain Research, 2020

Introduction: The ventral tegmental area (VTA), as one of the classical components of the brain r... more Introduction: The ventral tegmental area (VTA), as one of the classical components of the brain reward circuitry, shares large neural networks with the pain processing system. We previously showed the role of VTA dopamine receptors in modulation of lateral hypothalamus (LH)-induced antinociception in acute pain conditions. However, considering the fact that the neural systems involved in the mediation of tonic pain are not the same as those that mediate phasic pain. In the present study, we aimed to examine the role of intra-VTA dopamine receptors in LH-induced antinociceptive responses during tonic orofacial pain conditions. Methods: Male Wistar rats weighing 230-250 g were implanted with two separate cannulae into the LH and VTA on the same side. Different solutions of carbachol (62.5, 125 and 250 nM), as a non-selective cholinergic receptor agonist that activates the LH projecting neurons, were microinjected into the LH. In the other groups, D1-like dopamine receptor antagonist, SCH-23390 (0.25, 1 and 4 µg/03 µL saline) or D2-like dopamine receptor antagonist, Sulpiride (0.25, 1 and 4 µg/0.3 µL DMSO 12%) were microinjected into VTA, 5 min prior intra-LH carbachol (250 nM), then subjected to orofacial formalin test. Intra-LH carbachol microinjection dose-dependently attenuated biphasic orofacial pain. Results: Intra-VTA administration of SCH-23390 or Sulpiride dose-dependently decreased intra-LH carbachol-induced antinociception during both phases of orofacial formalin test with further effects in the late phase. Discussion: The findings suggest that chemical stimulation of the LH by carbachol possibly activates the orexin projecting neurons and subsequently, the VTA dopaminergic neurons involved in the orofacial pain modulation. Detecting such neural circuitry offers an alternative approach in the development of more efficient therapies for such debilitating pain conditions.

Brain Research, 2020

Dopamine is the predominant catecholamine neurotransmitter in the mammalian brain which has been ... more Dopamine is the predominant catecholamine neurotransmitter in the mammalian brain which has been shown to play a critical role in antinociceptive process. Previous studies have shown that the role of CA1 region of the hippocampus in antinociception induced by stimulation of the lateral hypothalamus (LH) through the dopaminergic system in tonic pain. In this study, we tried to assess the involvement of intra-hippocampal D1- and D2-like dopamine receptors in the LH stimulation-induced antinociception during the tail-flick test as an animal model of acute pain. Ninety-five male Wistar rats were unilaterally implanted with two separate cannulae into the LH and CA1. Animals received intra-CA1 infusion of SCH-23390 (0.25, 1 and 4 µg/rat), as a D1-like dopamine receptor antagonist and sulpiride (0.125, 0.25, 1 and 4 µg/rat), as a D2-like dopamine receptor antagonist, 2 min before intra-LH administration of carbachol (250 nM/rat). The antinociceptive effects of SCH-23390 and sulpiride were measured by using a tail-flick analgesiometer and represented as the maximal possible effect (%MPE). Also, the locomotion tracking apparatus was used to measure the locomotor activity of animals. Results showed that intra-CA1 administration of SCH-23390 or sulpiride could prevent the intra-LH carbachol-induced antinociception. This effect was a little more dominant after blocking the D2-like dopamine receptor in the CA1. These findings revealed that D1- and D2-like dopamine receptors within the CA1 play an important role in antinociceptive responses induced by chemical stimulation of the LH. It could be suggested that dopamine receptors in the CA1 were triggered by LH orexinergic projections.

Behavioural Pharmacology, 2019

Neurochemical Research, 2018

Reward-seeking and relapse to drug use are two characteristics of addiction and reports have indi... more Reward-seeking and relapse to drug use are two characteristics of addiction and reports have indicated the role of hippocampal structures in reward learning. To find the best ways of treatment, the understanding of the neurobiological mechanisms of reward and its involved factors is a must. For this reason, in the present study, we aimed to investigate the role of D1-and D2-like dopamine receptors and compared their activities in the CA1 region, focusing on the reinstatement induced by forced swim stress (FSS) or the combination of FSS and a subthreshold dose of morphine in extinguished morphine-CPP in rats. The rats were bilaterally implanted by two separate cannulas into the CA1 region. The animals received different doses of SCH23390 or sulpiride (0.5, 2, and 4 µg/0.5 µl vehicle/side) into the CA1 region on the reinstatement day and were tested for FSS-induced reinstatement or the combination of FSS and a subthreshold dose of morphine in separate groups. Our findings indicated that the D1-and D2-like receptor antagonists attenuated the reinstatement induced by the combination of FSS and the subthreshold dose of morphine. The behavioral results were more prominent in the groups of animals that received SCH23390 as compared to sulpiride. The data may suggest a role for the dopamine receptors in the CA1 region in relapse to drugs of abuse, which may be induced by exposure to a stressor.

Behavioral Neuroscience, 2019

Physiology & Behavior, 2019

Neurochemical Research, 2019

Role of the orexinergic system in pain modulation is well studied and involvement of the spinal o... more Role of the orexinergic system in pain modulation is well studied and involvement of the spinal orexin-1 receptors is well documented. In this study, we examined role of the spinal orexin-2 receptors in modulation of inflammatory pain in rat. Fifty-one adult male Wistar rats were implanted unilaterally with a guide cannula into the LH and intrathecal tubing in the lumbar space between L4 and L5. Chemical stimulation of LH by carbachol (250 nM/0.5 µL saline) induced remarkable analgesia during the two phases of formalin test and Intrathecal administration of different doses of TCS OX2 29 (10, 30 and 100 µM/ 0.5 µL DMSO) prior to LH stimulation, dose-dependently antagonized the antinociceptive effect of the LHstimulation during the two phases of formalin test. The effect size of the TCS OX2 29 was η 2 = 0.47 and η 2 = 0. 87 for the early and late phases of the test, respectively. Also, intrathecal administration of TCS OX2 29 alone (without stimulation of the LH) had no significant effect on formalin induced pain-related behaviors. Our results showed that spinal orexin-2 receptors are involved in modulation of the LH-stimulation induced analgesia in a persistent inflammatory pain model. These findings may suggest spinal orexin-2 receptors in particular and the orexin system in general as a useful therapeutic target for treatment of chronic pains.

Neuroscience Letters, 2018

Neuropeptides, 2018

Orexins are produced in the restricted regions of the lateral hypothalamus (LH). However, orexine... more Orexins are produced in the restricted regions of the lateral hypothalamus (LH). However, orexinergic receptors and projections are localized in wide regions like nucleus accumbens, ventral tegmental area, periaqueductal gray area and spinal cord which are involved in the pain modulation. This study was carried out to investigate the effects of intrathecal administration of orexin-1 receptor antagonist (SB-334867) in the spinal antinociception induced by intra-LH administration of carbachol (cholinergic receptor agonist) in both early and late phases of pain related behaviors in formalin test. In this study, pain-related behaviors (pain scores) were evaluated using the formalin test during 5-min block intervals for a 60-min period in seventy male Wistar rats were given SB-334867 (3, 10, 30 and 100 μM/10 μl) or vehicle (DMSO 12%; 10 μl) intrathecally following intra-LH administration of carbachol (250 nM/rat). Our data showed that intra-LH injection of carbachol attenuated the formal...

Behavioural Pharmacology, 2020

Relapsing to drugs of abuse is a challenging problem in treatment of addiction and stress is beli... more Relapsing to drugs of abuse is a challenging problem in treatment of addiction and stress is believed to be a major risk factor in relapse to drugs. The hippocampus region and dopamine signaling play a critical role in reward-related behaviors. The purpose of this study is to identify the involvement of D1- and D2-like receptors in the CA1 region of hippocampus in the reinstatement induced by a combination of food deprivation stress and a sub-threshold dose of morphine in extinguished morphine-conditioning place preference in rats. Adult male rats treated with one specific doses of SCH-23390 or sulpiride (0.5, 2 and 4 µg/0.5 µl vehicle/side) as D1- and D2-like receptors antagonists into the CA1 in separate groups, following the conditioning and extinction phase of morphine-conditioning place preference, before initiating the food deprivation stress on the last day of extinction. Then, the food deprived animals examined for reinstatement by injection of the sub-threshold dose of morphine (0.5 mg/kg, s.c.) on reinstatement day. Conditioning place preference scores and locomotor activities were recorded during test. Our results showed that combination of food deprivation stress and a sub-threshold dose of morphine induced the reinstatement of morphine-conditioning place preference. The induced reinstatement was decreased by two higher doses of SCH-23390 (2 and 4 µg/0.5 µl vehicle/side). However, the sulpiride (0.5, 2 and 4 µg/0.5 µl vehicle/side) could not reduce the reinstatement. Results showed that the role of D1-like receptor in the CA1 region was more prominent than D2-like receptor in reinstatement induced by food deprivation stress and re-exposure to morphine. Therefore the D1-like receptor in the CA1 might be a potential therapeutic target for treatment of opiate addiction.

Neurochemical Research

Lateral hypothalamus (LH) contains a large population of orexinergic neurons. Many studies have i... more Lateral hypothalamus (LH) contains a large population of orexinergic neurons. Many studies have investigated the function of these neurons and it is clear that they are involved in pain modulation. The nucleus accumbens (NAc) receives many orexinergic projections, and accumbal neurons express both receptors of orexin (OX1R and OX2R). In this study, we investigated the role of accumbal orexinergic receptors in the LH-induced antinociception during formalin-induced orofacial pain. Male adult Wistar rats weighing 230–250 g were used in this study. Cannulae were unilaterally implanted in their skull for microinjections. SB334867 (OX1 receptor antagonist) or TCS OX2 29 (OX2 receptor antagonist) at the doses of 3, 10 and 30 nM were injected into the NAc with/without intra-LH microinjection of carbachol (250 nM/rat). Carbachol was used for chemical stimulation of orexinergic neurons in the LH. Our results showed that intra-LH carbachol following injection of formalin into animals’ upper lip reduced nociception in both phases of formalin test. SB334867 and TCS OX2 29 were able to reduce LH-induced antinociception in both phases. Although the highest dose of SB334867 and TCS OX2 29 (30 nM) was effective in both phases, the TCS OX2 29 but not SB334867 at the dose of 10 nM could not reduce the antinociceptive responses induced by LH stimulation during the first (early) phase. It suggests that contribution of accumbal orexinergic receptors in the first phase of formalin test is more than the second (late) phase, and these results provide further evidence for the involvement of orexinergic system in the modulation of inflammatory orofacial pain.