Effects Of Endogenous Opioids Research Articles

Cellular and circuit diversity determines the impact of endogenous opioids in the descending pain modulatory pathway.

The descending pain modulatory pathway exerts important bidirectional control of nociceptive inputs to dampen and/or facilitate the perception of pain. The ventrolateral periaqueductal gray (vlPAG) integrates inputs from many regions associated with the processing of nociceptive, cognitive, and affective components of pain perception, and is a key brain area for opioid action. Opioid receptors are expressed on a subset of vlPAG neurons, as well as on both GABAergic and glutamatergic presynaptic terminals that impinge on vlPAG neurons. Microinjection of opioids into the vlPAG produces analgesia and microinjection of the opioid receptor antagonist naloxone blocks stimulation-mediated analgesia, highlighting the role of endogenous opioid release within this region in the modulation of nociception. Endogenous opioid effects within the vlPAG are complex and likely dependent on specific neuronal circuits activated by acute and chronic pain stimuli. This review is focused on the cellular heterogeneity within vlPAG circuits and highlights gaps in our understanding of endogenous opioid regulation of the descending pain modulatory circuits.

Evidence of alterations of Beta-endorphin levels and Mu-opioid receptor gene expression in bipolar disorder

Despite the well-recognized effects of endogenous opioids on mood and behavior, research on its role in bipolar disorder (BD) is still limited to small or anecdotal reports. Considering that Beta-endorphins (β-END) and Mu-opioid receptors (MOR), in particular, have a crucial activity in affective modulation, we hypothesized their alteration in BD. A cross-sectional study was conducted. We compared: (1) BD type I (BD-I) patients (n = 50) vs healthy controls (n = 27), (2) two BD-I subject subgroups: manic (MAN; n = 25) vs depressed (DEP; n = 25) subjects. Plasma levels of β-END and MOR gene expression in peripheral blood mononuclear cells were analyzed using ELISA Immunoassay qRT-PCR. We found that subjects with BD exhibited a significant upregulation of MOR gene expression and a decrease of β-END (p<0.0001 for both). MAN display higher MOR levels than DEP (p<0.001) and HC (p<0.0001). Plasma levels of β-END were lower in DEP compared to MAN (p<0.05) and HC (p<0.0001). The main limitations are the cross-sectional design and the lack of a group of euthymic subjects. Although preliminary, our results suggest a dysregulation of the endogenous opioid systems in BD. In particular, both MAN and DEP showed a reduction of β-END levels, whereas MAN was associated with MOR gene overexpression.

Effects of Endogenous Opioids on Pain Mechanism

Pain is defined as an unpleasant sensory and emotional experience, associated with potential tissue damage. Many studies have been conducted to reveal the effects of opioids on the pain mechanism. These studies have focused primarily on opioid peptides and opioid receptor agonists. In general, it is declared that dopaminergic, serotonergic, and glutaminergic systems as well as the opioid system are closely associated with pain. Morphine, an opioid type obtained from Papaver somniferum, has been used for pain relief for many years. Morphine and other exogenous opioids show their activity by binding to opioid receptors in living organisms. These receptors respond to opioid peptides expressed as inactive polypeptide hormones activated by proteolytic cleavage. These opioids found in living organisms are referred as endogenous opioids. Endogenous opioids and their peptides are expressed throughout the peripheral and central nervous system and regulate many different systems and functions. One of the main functions of the endogenous opioid peptide is to modulate our pain response through a descending pain modifying pathway. In light of this data, the mechanism of pain has been elucidated by studying the endogenous opioid mechanism. In this review, after the definition of pain, endogenous opioids and their receptors will be mentioned, the methodology and recent findings in pain research will be explained.

Isolating peripheral effects of endogenous opioids in modulating exertional breathlessness in people with moderate or severe COPD: a randomised controlled trial.

Question addressed by the studyEndogenous opioids (endorphins) have been reported to modulate exercise-induced breathlessness, but the relative contribution of peripheral opioid receptors has not been tested.Materials, participants and methodsThis was a double-blind, randomised, three-arm, cross-over trial in outpatients with spirometry-verified moderate to severe chronic obstructive pulmonary disease. Participants undertook an incremental symptom-limited treadmill test followed by five endurance treadmill tests at 75% of their maximal work rate; two tests for familiarisation and three tests 30 min after intravenous injection of either methylnaltrexone 0.3 mg·kg−1 (blocking peripheral opioid receptors only) or naloxone 0.1 mg·kg−1 (blocking both central and peripheral opioid receptors) or normal saline, in randomised order. The primary end-point was the regression slope between breathlessness intensity (0–10 numerical rating scale) and oxygen consumption (V′O2) during the walk tests, comparing methylnaltrexone and placebo using a paired t-test.Results17 participants completed the trial: median (range) 66 (55–82) years; 15 males; mean±sd forced expiratory volume (FEV1) 53.8±17.6% predicted; FEV1/forced vital capacity ratio 0.55±15.9. There was no statistically or clinically significant difference in the primary end-point (regression slope of breathlessness intensity and V′O2) for methylnaltrexone (p=0.498) or naloxone (p=0.804), compared to placebo. Secondary outcomes were similar between the three treatment groups, including peak and mean breathlessness intensity and unpleasantness, exercise capacity, endurance time and leg fatigue.Answer to the questionBlocking peripheral opioid receptors (methylnaltrexone) or peripheral and central opioid receptors (naloxone) did not appear to modulate breathlessness intensity nor exercise capacity when compared with placebo (no blockade).

The association between endogenous opioid function and morphine responsiveness: a moderating role for endocannabinoids.

We sought to replicate previous findings that low endogenous opioid (EO) function predicts greater morphine analgesia and extended these findings by examining whether circulating endocannabinoids and related lipids moderate EO-related predictive effects. Individuals with chronic low-back pain (n = 46) provided blood samples for endocannabinoid analyses, then underwent separate identical laboratory sessions under 3 drug conditions: saline placebo, intravenous (i.v.) naloxone (opioid antagonist; 12-mg total), and i.v. morphine (0.09-mg/kg total). During each session, participants rated low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects 4 times in sequence after incremental drug dosing. Mean morphine effects (morphine-placebo difference) and opioid blockade effects (naloxone-placebo difference; to index EO function) for each primary outcome (low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects) were derived by averaging across the 4 incremental doses. The association between EO function and morphine-induced back pain relief was significantly moderated by endocannabinoids [2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)]. Lower EO function predicted greater morphine analgesia only for those with relatively lower endocannabinoids. Endocannabinoids also significantly moderated EO effects on morphine-related changes in visual analog scale-evoked pain intensity (2-AG), drug liking (AEA and 2-AG), and desire to take again (AEA and 2-AG). In the absence of significant interactions, lower EO function predicted significantly greater morphine analgesia (as in past work) and euphoria. Results indicate that EO effects on analgesic and subjective responses to opioid medications are greatest when endocannabinoid levels are low. These findings may help guide development of mechanism-based predictors for personalized pain medicine algorithms.

T-lymphocyte-derived enkephalins reduce Th1/Th17 colitis and associated pain in mice.

Endogenous opioids, including enkephalins, are fundamental regulators of pain. In inflammatory conditions, the local release of opioids by leukocytes at the inflammatory site inhibits nociceptor firing, thereby inducing analgesia. Accordingly, in chronic intestinal Th1/Th17-associated inflammation, enkephalins released by colitogenic CD4+ T lymphocytes relieve inflammation-induced visceral pain. The present study aims to investigate whether mucosal T-cell-derived enkephalins also exhibit a potent anti-inflammatory activity as described for exogenous opioid drugs in Th1/Th17-associated colitis. The anti-inflammatory effects of endogenous opioids were investigated in both Th1/Th17-associated (transfer of CD4+CD45RBhigh T lymphocytes) and Th2-associated (oxazolone) colitis models in mice. Inflammation-induced colonic damage and CD4+ Tcell subsets were compared in mice treated or not treated with naloxone methiodide, a peripheral antagonist of opioid receptors. The anti-inflammatory activity of T-cell-derived enkephalins was further estimated by comparison of colitis severity in immunodeficient mice into which naïve CD4+CD45RBhigh T lymphocytes originating from wild-type or enkephalin-knockout mice had been transferred. Peripheral opioid receptor blockade increases the severity of Th1/Th17-induced colitis and attenuates Th2 oxazolone colitis. The opposite effects of naloxone methiodide treatment in these two models of intestinal inflammation are dependent on the potency of endogenous opioids to promote a Th2-type immune response. Accordingly, the transfer of enkephalin-deficient CD4+CD45RBhigh T lymphocytes into immunodeficient mice exacerbates inflammation-induced colonic injury. Endogenous opioids, including T-cell-derived enkephalins, promote a Th2-type immune response, which, depending on the context, may either attenuate (Th1/Th17-associated) or aggravate (Th2-associated) intestinal inflammation.

Experiencing neonatal maternal separation increased pain sensitivity in adult male mice: Involvement of oxytocinergic system

Early-life stress adversely affects the development of the brain, and alters a variety of behaviors such as pain in later life. In present study, we investigated how early-life stress (maternal separation or MS) can affect the nociceptive response later in life. We particularly focused on the role of oxytocin (OT) in regulating nociception in previously exposed (MS during early postnatal development) mice that were subjected to acute stress (restraint stress or RS). Further, we evaluated whether such modulation of pain sensation in MS mice are regulated by shared mechanisms of the OTergic and opioidergic systems. To do this, we assessed the underlying systems mediating the nociceptive response by administrating different antagonists (for both opioid and OTergic systems) under the different experimental conditions (control vs MS, and control plus RS vs MS plus RS). Our results showed that MS increased pain sensitivity in both tail-flick and hot-plate tests while after administration of OT (1μg/μl/mouse, i.c.v) pain threshold was increased. Atosiban, an OT antagonist (10μg/μl/mouse, i.c.v) abolished the effects of OT. While acute RS increased the pain threshold in control (and not MS) mice, treating MS mice with OT normalized the pain response to RS. This latter effect was reversed by atosiban and/or naltrexone, an opioid antagonist (0.5μg/μl/mouse, i.c.v) suggesting that OT enhances the effect of endogenous opioids. OTergic system is involved in mediating the nociception under acute stress in mice subjected to early-life stress and OTergic and opioidergic systems interact to modulate pain sensitivity in MS mice.

Event-related potentials in performance monitoring are influenced by the endogenous opioid system

Recent research suggests that not only the dopamine neurotransmitter system but also the endogenous opioid system is involved in performance monitoring and the generation of prediction error signals. Heightened performance monitoring is also associated with psychopathology such as internalizing disorders. Therefore, the current study investigated the potential link between the functional opioid peptide prodynorphin (PDYN) 68bp VNTR genetic polymorphism and neuronal correlates of performance monitoring.To this end, 47 healthy participants genotyped for this polymorphism, related to high-, intermediate-, and low-expression levels of PDYN, performed a choice-reaction task while their electroencephalogram (EEG) was recorded. On the behavioural level, no differences between the three PDYN groups could be observed. EEG data, however, showed significant differences. High PDYN expression individuals showed heightened neural error processing indicated by higher ERN amplitudes, compared to intermediate and low expression individuals. Later stages of error processing, indexed by late Pe amplitudes, and stimulus-driven conflict processing, indexed by N2 amplitudes, were not affected by PDYN genotype.The current results corroborate the notion of an indirect effect of endogenous opioids on performance monitoring, probably mediated by the mesencephalic dopamine system. Overall, enhanced ERN amplitudes suggest a hyper-active performance monitoring system in high PDYN expression individuals, and this might also be an indicator of a higher risk for internalizing disorders.

Antagonism of substance P and perception of breathlessness in patients with chronic obstructive pulmonary disease

The objective of this study was to investigate whether substance P, an excitatory neuropeptide, modulates the perception of breathlessness by administering aprepitant, a selective antagonist that blocks neurokinin (NK)-1 receptor signaling.Individual targeted resistive load breathing (RLB) was used to provoke breathlessness.In Study 1, sixteen patients (age, 70±6 years) with chronic obstructive pulmonary disease (COPD) reported similar ratings of breathlessness during RLB between oral aprepitant (125mg) and placebo. After aprepitant, but not with placebo, there were significant increases in blood levels of substance P (+54±39%) and beta-endorphin (+27±17%). A similar design was used in Study 2 except that naloxone (10mg) was administered intravenously prior to RLB to block any effect of endogenous opioids. Nine patients with COPD reported comparable breathlessness ratings during RLB between aprepitant and placebo.Our results do not support a role for the substance P-NK-1 pathway in the perception of breathlessness in patients with COPD. With selective antagonism of NK-1 signaling, there was co-transmission of substance P and beta-endorphin neuropeptides.

Effect of Increased Blood Levels of β-Endorphin on Perception of Breathlessness

Although opioid receptors are expressed broadly in the CNS and in peripheral sensory nerve endings including bronchioles and alveolar walls of the respiratory tract, it is unknown whether the modulatory effect of endogenous opioids on breathlessness occurs in the CNS or in the peripheral nervous system. The purpose of this investigation was to examine whether increased blood levels of β-endorphin modify breathlessness by a putative effect of binding to peripheral opioid receptors in the respiratory tract. Twenty patients with COPD (10 women and 10 men; age, 70 ± 8 years) inspired through resistances during practice sessions to identify an individualized target load that caused ratings of intensity and unpleasantness of breathlessness ≥ 50 mm on a 100-mm visual analog scale. At two interventions, blood levels of β-endorphin and adrenocorticotropic hormone (ACTH) were measured, ketoconazole (600 mg) or placebo was administered orally, and patients rated the two dimensions of breathlessness each minute during resistive load breathing (RLB). By inhibiting cortisol synthesis, ketoconazole led to significant increases in β-endorphin (mean change, 20% ± 4%) and ACTH (mean change, 21% ± 4%) compared with placebo. The intensity and unpleasantness ratings of breathlessness and the endurance time during RLB were similar in the two interventions. The previously demonstrated modulatory effect of endogenous opioids on breathlessness appears to be mediated by binding to receptors within the CNS rather than to peripheral opioid receptors in the respiratory tract. An alternative explanation is that the magnitude of the β-endorphin response is inadequate to affect peripheral opioid receptors. ClinicalTrials.gov; No.: NCT01378520; URL: www.clinicaltrials.gov.

Emotional and Physical Distress Relief Using a Novel Endorphinergic Formulation

While the endogenous opioid system has generally been associated with regulation of pain, it also modulates the experience of distress and may play a central role in many psychiatric and neurodevelopmental disorders. Decades of preclinical research on the analgesic effects of endogenous opioids, i.e., endorphins, suggests that opioid receptors have plastic bimodal (inhibitory/excitatory) properties that may explain conflicting findings in clinical research. An exploratory study with 60 healthy volunteer participants, using a cold pressor-induced pain paradigm, found evidence that a combination of a nutraceutical agent that enhances endorphin release (Endorphin Enhancer) with one that switches opioid receptors from an excitatory to inhibitory mode (Opioid Receptor Switcher) not only increases pain tolerance but also reduces emotional and physical distress. This discovery led to clinical application of a critically formulated endorphinergic treatment in 203 case studies over a two-year period. Findings revealed the remarkable clinical efficacy and safety of this treatment in the relief of chronic emotional and physical distress, including anxiety, anger, depression, cravings, and hyperalgesia, as well as enhancement of well-being, productivity, mental clarity, relationships, and an adaptive response to life’s stresses. These studies provide new insights into the role of endogenous opioid system imbalances in the development, treatment, and prevention of dysfunctional emotional and physical distress. We postulate that an Endorphinergic Distress Syndrome (EDS) consists of abnormal endorphin levels together with opioid receptors predominately in their excitatory mode. EDS may account for many core distress symptoms associated with chronic anxiety, addictions, pain, as well as affective personality, autism spectrum, attention-deficit, and distress-related medical problems. Our research has led to new endorphinergic formulations, combining Endorphin Enhancers, such as caffeine, with Opioid Receptor Switchers, such as n-acetylcysteine, for the relief of emotional and physical distress. Our studies also provide a novel method to reverse the anxiogenic effects of caffeine and related hyperexcitatory substances.

Effects of estrogen and opioid blockade on blood pressure reactivity to stress in postmenopausal women

Estrogen may influence coronary heart disease risk in women through the effects of endogenous opioids on autonomic control of blood pressure. In a randomized, placebo-controlled trial, we examined the combined effects of estrogen and the opioid antagonist, naltrexone, on blood pressure responses to psychological stress in 42 postmenopausal women. After 3months of estrogen or estrogen plus progestin (hormone replacement therapy; n=27) or placebo replacement, participants completed a mental arithmetic task after administration of .7mg/kg oral naltrexone or placebo. Systolic blood pressure (SBP), diastolic blood pressure, mean arterial pressure and heart rate (HR) were measured at rest and during the arithmetic stressor. Stress produced significant increases in circulatory measures regardless of estrogen condition or opioid blockade (p's<.001). Interestingly, there was an estrogen by naltrexone interaction on SBP reactivity scores [F(1,38)=4.36, p<.05], where women on estrogen with intact opioid receptors showed the largest SBP responses to stress, compared with all other conditions. This is consistent with some studies of premenopausal women, suggesting that estrogens may alter opioid function during stress. The interaction between estrogen and endogenous opioids may explain sex differences in opioid effects on stress reactivity in younger premenopausal women.

Ontogeny of the Pain

The article gives an overview of developmental aspects of the ontogeny of pain both in experimental models and in children. The whole article is devoted to the ontogenesis in pain perception and the possible influence on it. The role of endogenous opioids on the development of pain and other important substances such as serotonin, nerve growth factor (NGF) and nicotine are mentioned. There are also important differences of the ontogenesis of thermal and mechanical nociceptive stimulation. The physiological and pathophysiological findings are the backgrounds for principles of treatment, taking into account the special status of analgesics during ontogeny. In particular there are mentioned the special effects of endogenous opioids and especially morphine. It describes the role of vitamin D and erythropoietin during the development of pain perception. This article also mentioned the critical developmental periods in relation to the perception of pain. The attention is paid to stress and immunological changes during the ontogeny of pain. Another important role is played by microglia. The work is concluded by some statements about the use of physiological and pathophysiological findings during the treatment of pain in pediatric practice. Codein analgesia is also described because codein starts to be very modern drug with the dependence.

Neuromodulatory Effect of Endogenous Opioids on the Intensity and Unpleasantness of Breathlessness during Resistive Load Breathing in COPD

Background: Endogenous opioids are naturally occurring peptides released by the brain in response to noxious stimuli. Although these naturally occurring peptides modulate pain, it is unknown whether endogenous opioids affect the perception of breathlessness associated with a specific respiratory challenge. The hypothesis is that intravenous administration of naloxone, used to block opioid signaling and inhibit neural pathways, will increase ratings of breathlessness during resistive load breathing (RLB) in patients with chronic obstructive pulmonary disease (COPD). Methods: Fourteen patients with COPD (age, 64 ± 9 years) inspired through resistances during practice sessions to identify an individualized target load that caused ratings of intensity and/or unpleasantness of breathlessness ≥ 50 mm on a 100 mm visual analog scale. At two intervention visits, serum beta-endorphins were measured, naloxone (10 mg/25 ml) or normal saline (25 ml) was administered intravenously, and patients rated the two dimensions of breathlessness each minute during RLB. Results: Patient ratings of intensity (p = 0.0004) and unpleasantness (p = 0.024) of breathlessness were higher with naloxone compared with normal saline. Eleven patients (79%) reported that it was easier to breathe during RLB with normal saline (p = 0.025). RLB led to significant increases in serum beta-endorphin immunoreactivity and decreases in inspiratory capacity. There were no significant differences in physiological responses between interventions. Conclusions: Endogenous opioids modulate the intensity and the unpleasantness of breathlessness in patients with COPD. Differences in breathlessness ratings between interventions were clinically relevant based on the patients’ global assessment.

Exogenously administered opioids contract the female rat intrinsic urethral sphincter in vivo

Previous studies have reported immunoreactive opioid nerve fibers in the detrusor and lower urinary tract sphincters. However, there is a paucity of in vivo studies demonstrating the direct effect of endogenous opioids in these structures. In the present study, we investigated the contractile actions of intra-arterially administered exogenous Dynorphin-A, Met-enkephalin, Leu-enkephalin, morphine, and the opioid antagonist naltrexone on the female rat intrinsic urethral sphincter in vivo. Intraurethral pressure was recorded by a catheter placed at the maximum pressure zone of the intrinsic urethral sphincter in anesthetized female Sprague-Dawley rats. The effects of different opioids were studied and expressed as means and as percentages of pressure change (cmH(2)O) of the baseline intraurethral pressure. Dynorphin-A, Met-enkephalin, and Leu-enkephalin evoked rapid, long-lasting contractile effects on the female rat urethra. The greatest intraurethral pressure increase was evoked by Dynorphin-A (89.2 +/- 15.3%). For Met-enkephalin, intraurethral pressure increased by 70.2 +/- 21.8% and for Leu-enkephalin, the pressure increase was 60.6 +/- 20%. Morphine, however, evoked inconsistent intraurethral pressure changes, increasing the urethral pressure in three subjects and lowering the pressure in the remaining six subjects. The opioid antagonist naltrexone reduced the intraurethral pressure by a mean of -19.0 +/- 5.8%. Results of the present study suggest that endogenous opioids by their contractile action on the intrinsic urethral sphincter may play a role in the control of continence in rats, additional to cholinergic and noradrenergic pathways.

940 The Anti-Nociceptive Effects of Endogenous Opioids in Chronic DSS Colitis

940 The Anti-Nociceptive Effects of Endogenous Opioids in Chronic DSS Colitis

Preference or fat? Revisiting opioid effects on food intake

It is well established that opioid signaling in the central nervous system constitutes a powerful stimulus for food intake. The role of opioids in determining food preference, however, is less well defined. Opioids have been proposed to promote intake of preferred foods, or, alternatively, to preferentially increase consumption of fat. In the present manuscript, I comprehensively review results from previous studies investigating this issue. Data from these studies suggests a mechanism for opioid action that may reconcile the previously proposed hypotheses: opioid effects on food intake do appear to be largely specific for fat consumption, but individual animals' sensitivity to this effect may be dependent on baseline food preferences. In addition, I highlight the possibility that the selectivity of endogenous opioid effects may importantly differ from that of exogenous agonists in the degree to which baseline preferences, rather than macronutrient intake, are altered. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.

The stimulative effects of endogenous opioids on endothelial cell proliferation, migration and angiogenesis in vitro

The opioid peptides modulate extensive bioactivities, including pain, cardiovascular response, development and further responses. In the present study, the stimulative effects of endogenous opioid peptides on angiogenesis are evaluated in the proliferation, migration, adhesion and tube formation assays of the human umbilical vein endothelial cell (HUVEC) for the first time. Endomorphin-1, endomorphin-2 and deltorphin I at physiological concentrations could stimulate HUVECs proliferation, migration, adhesion and tube formation in a dose dependent manner; whereas, they exhibited the cytotoxic effects on HUVECs at the higher doses in these assays. Naloxone, the nonselective opioid receptor antagonist, did not influence angiogenesis when it was administrated on its own; but it could antagonize the stimulative effects of the opioid peptides on angiogenesis when it was administrated in combination with the opioid peptides. Taken altogether, the results suggested that endogenous opioid peptides (endomorphin-1 and -2 and deltorphin I) stimulated angiogenesis at the cellular level, and these effects were mediated by the opioid receptors. These data are significant for potential clinical implementation in future.

Effects of endogenous opioids on electrophysiology of hippocampus during the estrous cycle of adult female rat

Event Abstract Back to Event Effects of endogenous opioids on electrophysiology of hippocampus during the estrous cycle of adult female rat Minoo Mahmoodi1*, Siamak Shahidi2, A. Komaki2 and N. Batebi2 1 Department of Biology, Islamic Azad University, Hamadan Branch, Iran 2 Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Iran Introduction: Endogenous opioids play critical role on learning and memory processing. Their levels fluctuate during reproductive cycle. In addition, learning and memory change during reproductive cycle. There is no report to indicate that fluctuation of endogenous opioids involve in the fluctuation of learning and memory during estrous cycle. As hippocampal synaptic plasticity is consider as a cellular model of learning and memory, the aim of this study was to define the role of endogenous opioids on electrophysiological characteristics hippocampal dentate gyrus during the rat estrous cycle. Materials and Methods: The proestrus and estrus phase adult female rats were anesthetized with urethane and placed in a stereotaxic device for surgery and recording. The recording and stimulating electrodes were positioned in the granular cells of dentate gyrus and perforant pathway, respectively. After ensuring a steady state baseline response, single i.p injection of saline or naloxone was done. Then, paired pulses stimuli were delivered to induce recurrent inhibition. After that, long term potentiation (LTP) was induced using high-frequency stimuli. The population spike (PS) amplitude and the slope of excitatory post synaptic potentials (EPSP) were compared between these groups. Results: There was a significant increase in the PS of proestrus rats following naloxone treatment. PS of others groups did not show significant change. Following high frequency stimulation, the augmentation of EPSP of estrus phase saline treated rats were significantly less than other groups. High frequency stimulation potentiated the PS in the proestrus phase naloxone treated rats significantly more than other groups. Also, naloxone decrease the pair pulses inhibition index in the proestrus phase rats but not in the other groups. Discussion: Naloxone has modulatory effects on the hippocampal dentate gyrus activity during estrous cycle. They increase dentate gyrus granular cells activity and augment LTP induction in the proestrus phase rat. This effect may due to decreasing the GABAergic interneuron activitiy in the dentate gyrus. Also, it improves LTP induction (but noot basal activity) of hippocampal neurons in the estrus phase rat. This effect of naloxone may due to direct action on the dentate gyrus hippocampal cells. Conference: 10th International Conference on Cognitive Neuroscience, Bodrum, Turkey, 1 Sep - 5 Sep, 2008. Presentation Type: Poster Presentation Topic: Neuronal Plasticity Citation: Mahmoodi M, Shahidi S, Komaki A and Batebi N (2008). Effects of endogenous opioids on electrophysiology of hippocampus during the estrous cycle of adult female rat. Conference Abstract: 10th International Conference on Cognitive Neuroscience. doi: 10.3389/conf.neuro.09.2009.01.310 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 10 Dec 2008; Published Online: 10 Dec 2008. * Correspondence: Minoo Mahmoodi, Department of Biology, Islamic Azad University, Hamadan Branch, Hamadan, Iran, minoomahmoodi@yahoo.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Minoo Mahmoodi Siamak Shahidi A. Komaki N. Batebi Google Minoo Mahmoodi Siamak Shahidi A. Komaki N. Batebi Google Scholar Minoo Mahmoodi Siamak Shahidi A. Komaki N. Batebi PubMed Minoo Mahmoodi Siamak Shahidi A. Komaki N. Batebi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Role of endogenous opioids in modulating HSC activity in vitro and liver fibrosis in vivo

Background:Endogenous opioids modulate the growth of nervous and non-nervous cells. Hepatic stellate cells (HSCs) are the main cell phenotype involved in liver fibrogenesis, display molecular markers of neuronal cells and...