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Opioid agonists are used in clinic for pain management, however this application is challenged by development of tolerance and dependence following prolonged exposure. Various approaches have been suggested to address this concern, however, there is still no consensus among the researchers. Neural processing of sleep and nociception are co-regulated through shared brain regions having bidirectional interplays. Thus, we aimed to investigate whether application of REM sleep deprivation (REM-SD) could affect morphine analgesic tolerance and dependence. To this end, adult male rats underwent sleep deprivation during light and dark phases (LSD and DSD, respectively) using the inverted flower pot method and then tolerance and dependence was induc
Early life stress can serve as one of the principle sources leading to individual differences in confronting challenges throughout the lifetime. Maternal deprivation (MD), a model of early life stress, can cause persistent alterations in brain function, and it may constitute a risk factor for later incidence of drug addiction. It is becoming more apparent that early life MD predisposes opiate abuse in adulthood. Although several behavioral and molecular studies have addressed this issue, changes in electrophysiological features of the neurons are yet to be understood. The lateral paragigantocellularis (LPGi) nucleus, which participates in the mediation of opiate dependence and withdrawal, may be susceptible to modifications following MD. Th
Early life stress can serve as one of the principle sources leading to individual differences in confronting challenges throughout the lifetime. Maternal deprivation (MD), a model of early life stress, can cause persistent alterations in brain function, and it may constitute a risk factor for later incidence of drug addiction. It is becoming more apparent that early life MD predisposes opiate abuse in adulthood. Although several behavioral and molecular studies have addressed this issue, changes in electrophysiological features of the neurons are yet to be understood. The lateral paragigantocellularis (LPGi) nucleus, which participates in the mediation of opiate dependence and withdrawal, may be susceptible to modifications following MD. Th
Orexin neuropeptides are implicated in the expression of morphine dependence. Locus coeruleus (LC) nucleus is an important brain area involving in the development of withdrawal signs of morphine and contains high expression of orexin type 1 receptors (OX1Rs). Despite extensive considerations, effects of immediate inhibition of OX1Rs by a single dose administration of SB-334867 prior to the naloxone-induced activation of LC neurons remains unknown. Therefore, we examined the direct effects of OX1Rs acute blockade on the neuronal activity of the morphine-dependent rats which underwent naloxone administration. Adult male rats underwent subcutaneous administration of 10 mg/kg morphine (two times/day) for a ten-day period. On the last day of e
Adolescence is the transitional period between childhood and adulthood and a critical period in brain development. Adolescence in humans is also associated with increased expression of risk-taking behaviors. Epidemiological and clinical studies, for example, show a surge of drug abuse and raise the hypothesis that the adolescent brain undergoes critical changes resulting in diminished control. Determining how substance abuse during this critical period might cause long-term neurobiological changes in cognition and behavior is therefore critically important. The present work aims to provide an evaluation of the transgenerational and multi-generational phenotypes derived from parent animals exposed to drugs of abuse only during their adolesce
Chronic pain is recognized as an important problem in communities. The Locus coeruleus (LC) with extensive ascending and descending projections has a critical role in modulating pain. Some studies indicate how the locus coeruleus-noradrenaline system can remain more active after nociceptive stimulation. In the present study, we examined whether formalin-induced inflammatory pain may affect the electrophysiological properties of LC neurons after 24 hours. Inflammatory pain was induced by a subcutaneous injection of 2% formalin (10 ?l) into the hind paw of 2-3 week-old male Wistar rats. After 24 hours, horizontal slices of brain stem containing the locus coeruleus were prepared and whole-cell patch-clamp recordings were carried out on L
Over the past decade, many studies have indicated that adolescence is a critical period of brain development and maturation. The refinement and maturation of the central nervous system over this prolonged period, however, makes the adolescent brain highly susceptible to perturbations from acute and chronic drug exposure. Here we review the preclinical literature addressing the long-term consequences of adolescent exposure to common recreational drugs and drugs-of-abuse. These studies on adolescent exposure to alcohol, nicotine, opioids, cannabinoids and psychostimulant drugs, such as cocaine and amphetamine, reveal a variety of long-lasting behavioral and neurobiological consequences. These agents can affect development of the prefrontal co
Objective (s):Adipose-derived stem cells (ADSCs), with suitable and easy access, are multipotential cells that have the ability for differentiation into other mesodermal and transdifferentiate into neural phenotype cells. In this study, Lithium chloride (LiCl) was used for in vitro transdifferentiation of rat ADSCs into neuron-like cells (NLCs).Materials and Methods:ADSCs were isolated from the rats’ perinephric region using Dulbecco΄ s Modified Eagle΄ s Medium (DMEM) with Fetal Bovine Serum (FBS), cultured for 3 passages, characterized by flowcytometry and differentiation into adipogenic and osteogenic phenotypes. The ADSCs were exposed to 0.1, 0.5, 1, 1.5, 2, 5, and 10 millimolar (mM) LiCl without serum for 24 hr. The optimum dose of
Accumulating evidence support the critical role of endogenous orexin system in modulation of various physiological functions. Among these, regulation of pain and wakefulness have extensively been investigated, however, by independent series of studies each focusing a distinct side. It is now well established that orexins induce potent analgesic effect via affecting their receptors within several specific brain structures. These mainly include locus coeruleus (LC), lateral paragigantocellularis (LPGi), ventral tegmental area (VTA), dorsal raphe nucleus (DRN), periaquiductal gray (PAG) and tuberomammillary nuclei (TMN). On the other hand, increased activity of orexinergic neurons enhances general wakefulness. Interestingly, a review of litera
Objectives: The major problem in maintenance treatment of opioid use disorder is craving and relapse. The utilization of herbal compounds and complementary therapy for treatment of disease and addiction has been widely expanding. Considering the significant effect of Hab-o Shefa in detoxification phase, this clinical trial has explored the influence of this compound on maintenance treatment of opioid-dependent patients. This product is made of four herbs, including Datura stramonium L., Rheum palmatum L., Zingiber officinale Roscoe, and Acacia senegal L. Design: The authors conducted a two-group parallel randomized double-blind clinical trial on 81 opioid-dependent patients within 12 weeks. After medically assisted detoxification, participa
The mechanisms involved in the anti-seizure effects of low-frequency stimulation (LFS) have not been completely determined. However, Gi-protein-coupled receptors, including D2-like receptors, may have a role in mediating these effects. In the present study, the role of D2-like receptors in LFS’ anti-seizure action was investigated. Rats were kindled with semi-rapid (6 stimulations per day), electrical stimulation of the hippocampal CA1 area. In LFS-treated groups, subjects received four trials of LFS at 5 min, 6 h, 24 h, and 30 h following the last kindling stimulation. Each LFS set occurred at 5 minute intervals, and consisted of 4 trains. Each train contained 200, 0/1 ms long, monophasic square wave pulses at 1 Hz. Haloperidol (D2-like