Pharmacology Biochemistry and Behavior最新文献

{"title":"Sleep debt-induced anxiety and addiction to substances of abuse: A narrative review","authors":"Aline Ostos-Valverde ,&nbsp;Andrea Herrera-Solís ,&nbsp;Alejandra E. Ruiz-Contreras ,&nbsp;Mónica Méndez-Díaz ,&nbsp;Oscar E. Prospéro-García","doi":"10.1016/j.pbb.2024.173874","DOIUrl":"10.1016/j.pbb.2024.173874","url":null,"abstract":"<div><p>Substance Use Disorder (SUD) has been conceptualized as an outcome of a dysregulated reward system. However, individuals with SUD suffer from anxiety with an intensity depending on the abstinence period length. This review discusses the role of anxiety as a major contributor to the initiation and perpetuation of SUD, and its dependence on an up-regulated defense-antireward system. In addition, it is discussed that sleep debt, and its psychosocial consequences, promote anxiety, contributing to SUD generation and maintenance. Healthy sleep patterns can be disrupted by diverse medical conditions and negative psychosocial interactions, resulting in accumulated sleep debt and anxiety. Within this narrative review, we discuss the interplay between the motivation-reward and defense-antireward systems, framing the progression from recreational drug use to addiction. This interplay is nuanced by sleep debt-induced anxiety and its psychosocial consequences as contributory vulnerability factors in the genesis of addiction.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173874"},"PeriodicalIF":3.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142173518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-based differences in neuropsychiatric symptoms are due to estradiol/ERα-dependent transcriptional regulation via the modulation of steroid levels by sirolimus","authors":"Makiko Koike-Kumagai ,&nbsp;Manabu Fujimoto ,&nbsp;Mari Wataya-Kaneda","doi":"10.1016/j.pbb.2024.173875","DOIUrl":"10.1016/j.pbb.2024.173875","url":null,"abstract":"<div><p>The sex of the patient often affects the prevalence, progression, and severity of many psychiatric disorders. The incidence, progression, and severity of Parkinson's disease and Alzheimer's disease, the most common neurodegenerative diseases, also differ between the sexes. Sex differences in autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and anxiety are also observed in tuberous sclerosis complex (TSC). Neuropsychiatric symptoms are one of the most important manifestations of TSC, and the multiple neuropsychiatric symptoms are collectively referred to as TSC-associated neuropsychiatric disorders (TAND). We created TSC model mice (Tsc2 conditional knockout [cKO] mice) that developed epilepsy and TAND. Sex-based differences were observed for hyperactivity and cognitive dysfunctions in Tsc2 cKO mice with TAND, indicating more severe symptoms in female mice than in male mice. TSC is thought to be caused by the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1), and mTORC1 inhibitors improve almost all TSC symptoms. Treatment with sirolimus, an mTORC1 inhibitor, improved TAND in Tsc2 cKO mice. We aimed to elucidate the mechanism underlying sex-based differences in TAND using Tsc2 cKO mice and sirolimus. We found that estradiol (E2) and estrogen receptor (ER)α are involved in sex differences in neuropsychiatric symptoms, and discovered a novel function of sirolimus. We showed that sirolimus ameliorated TAND by modulating brain steroid levels and regulating E2/ERα-dependent transcriptional activation. This indicates sirolimus may be beneficial for the treatment of TAND as well as diseases caused by sex-based differences and steroid levels.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173875"},"PeriodicalIF":3.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142151623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult and adolescent antipsychotic exposure increases delay discounting and diminishes behavioral flexibility in male C57BL/6 mice","authors":"Dalisa R. Kendricks,&nbsp;Carleigh Morrow,&nbsp;D. Austin Haste,&nbsp;M. Christopher Newland","doi":"10.1016/j.pbb.2024.173866","DOIUrl":"10.1016/j.pbb.2024.173866","url":null,"abstract":"<div><p>Second-generation antipsychotics are frequently prescribed to adolescents, but the long-term consequences of their use remain understudied. These medications work via monoamine neurotransmitter systems, especially dopamine and serotonin, which undergo considerable development and pruning during adolescence. Dopamine and serotonin are linked to a wide host of behaviors, including impulsive choice and behavioral plasticity. In a murine model of adolescent antipsychotic use, male C57BL/6 mice were exposed to either 2.5 mg/kg/day risperidone or 5 mg/kg/day olanzapine via drinking water from postnatal days 22–60. To determine whether the adolescent period was uniquely sensitive to antipsychotic exposure, long-term effects on behavior were compared to an equivalently exposed group of adults where mice were exposed to 2.5 mg/kg risperidone from postnatal days 101–138. Motor activity and body weight in adolescent animals were assessed. Thirty days after exposure terminated animal's behavioral flexibility and impulsive choice were assessed using spatial discrimination reversal and delay discounting. Antipsychotic exposure produced a modest change in behavior flexibility during the second reversal. There was a robust and reproducible difference in impulsive choice: exposed animals devalued the delayed alternative reward substantially more than controls. This effect was observed both following adolescent and adult exposure, indicating that an irreversible change in impulsive choice occurs regardless of the age of exposure.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173866"},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine mediates a directionally opposite correlation between empathy and the reinforcing effects of amphetamine and gambling in people with gambling disorder vs. healthy controls","authors":"Martin Zack ,&nbsp;Arian Behzadi ,&nbsp;Candice Biback ,&nbsp;Bindiya Chugani ,&nbsp;Dan DiGiacomo ,&nbsp;Tim Fang ,&nbsp;Sylvain Houle ,&nbsp;Aditi Kalia ,&nbsp;Daniela Lobo ,&nbsp;Doris Payer ,&nbsp;Constantine X. Poulos ,&nbsp;Pablo M. Rusjan ,&nbsp;Kelly Smart ,&nbsp;Daniel Tatone ,&nbsp;Jerry Warsh ,&nbsp;Alan A. Wilson ,&nbsp;James L. Kennedy","doi":"10.1016/j.pbb.2024.173865","DOIUrl":"10.1016/j.pbb.2024.173865","url":null,"abstract":"<div><div>Understanding the relationship between empathy, subjective effects of addictive reinforcers and dopamine function in people with gambling disorder (PGD) vs. healthy controls (HCs) may inform GD treatment. The current investigation addressed this issue via retrospective analysis of data from three studies using amphetamine and a slot machine (SLOTS) as reinforcers in PGD and HCs. The Empathy scale of Eysenck's Impulsiveness Questionnaire assessed trait Empathy. The Gamblers Beliefs Questionnaire assessed cognitive distortions. The Eysenck Lie scale assessed socially desirable responding. PET scans quantified dopamine receptor expression and amphetamine-induced dopamine release in Study 1. Pre-treatment with the D2-receptor (D2R)-preferring antagonist, haloperidol or D1R-D2R antagonist, fluphenazine before SLOTS tested the role of D2 autoreceptors and post-synaptic D2R in Study 2. Pre-treatment with the multi-system indirect dopamine agonist, modafinil before SLOTS assessed the reliability of correlations in PGD. Striatal D2R expression predicted greater Empathy and lower amphetamine ‘Liking’ in HCs, and predicted greater symptom severity in PGD. Empathy predicted lower ‘Exciting’ effects of SLOTS under placebo in HCs; no correlation emerged under either antagonist. Relative to placebo, haloperidol decreased, whereas fluphenazine increased, the positive correlation between Empathy and Exciting effects of SLOTS in PGD. Modafinil markedly reduced the positive correlation between Empathy and Exciting effects of SLOTS seen under placebo in PGD. Empathy predicted greater cognitive distortions in PGD in all studies. Lie scale variance influenced several primary effects. Prior research linking the insula with Empathy, reactivity to interoceptive signals for risky rewards (uncertainty), and cognitive distortions, provides a parsimonious account for these results.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173865"},"PeriodicalIF":3.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous use of venlafaxine and calcium channel blockers on tolerance to morphine: The role of mitochondrial damage and oxidative stress in the brain","authors":"Asma Soleimanii ,&nbsp;Faezeh Fallah ,&nbsp;Behnam Ghorbanzadeh ,&nbsp;Ali Akbar Oroojan ,&nbsp;Neda Amirgholami ,&nbsp;Soheila Alboghobeish","doi":"10.1016/j.pbb.2024.173864","DOIUrl":"10.1016/j.pbb.2024.173864","url":null,"abstract":"<div><h3>Background</h3><p>One of the reasons for tolerance to morphine is increased oxidative stress and dysfunction of cell mitochondria in the hippocampus. Venlafaxine and calcium channel blockers can protect mitochondrial function. The investigation of the role of mitochondrial damage and oxidative stress in the simultaneous use of venlafaxine and calcium channel blockers on the acute analgesic effects of morphine and the induction of tolerance to its effects in mice was assessed.</p></div><div><h3>Method</h3><p>In this experimental study, to induce tolerance to morphine, NMRI mice were treated with 50 mg/kg morphine for three consecutive days and 5 mg/kg morphine on the fourth day. Venlafaxine (20 mg/kg) alone or in combination with calcium channel blockers, nimodipine (10 mg/kg), and diltiazem (40 mg/kg) was administered 30 min before morphine, and the hot plate test was used. Then, hippocampal mitochondria were isolated by differential centrifugation method, and the levels of mitochondrial dehydrogenase activity, mitochondrial membrane potential, mitochondrial ROS production rate, as well as the content of glutathione and malondialdehyde in hippocampal mitochondria, were measured.</p></div><div><h3>Results</h3><p>The administration of venlafaxine-nimodipine and venlafaxine-diltiazem increased morphine's acute analgesic effects (<em>P</em> &lt; 0.05) and reduced the induction and expression of tolerance to the analgesic effects of morphine (P &lt; 0.05). Morphine significantly decreased MTT and GSH and increased MDA, mitochondrial membrane damage, and ROS compared to the control group (<em>P</em> &lt; 0.01). Injection of venlafaxine-nimodipine and also venlafaxine-diltiazem 30 min before morphine can improve these alterations (<em>P</em> &lt; 0.05).</p></div><div><h3>Discussion and conclusion</h3><p>Our data showed that the simultaneous use of venlafaxine with calcium channel blockers could increase the acute analgesic effects of morphine and reduce the induction and expression of tolerance to it. Also, the preventive and protective roles of simultaneous administration of venlafaxine and calcium channel blockers on morphine-induced mitochondrial oxidative stress and damage during the tolerance test were achieved.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173864"},"PeriodicalIF":3.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAAR1 and 5-HT1B receptor agonists attenuate autism-like irritability and aggression in rats prenatally exposed to valproic acid","authors":"Lien Wang ,&nbsp;Erin A. Clark ,&nbsp;Lynsey Hanratty ,&nbsp;Kenneth S. Koblan ,&nbsp;Andrew Foley ,&nbsp;Nina Dedic ,&nbsp;Linda J. Bristow","doi":"10.1016/j.pbb.2024.173862","DOIUrl":"10.1016/j.pbb.2024.173862","url":null,"abstract":"<div><p>Despite the rising prevalence of autism spectrum disorder (ASD), there remains a significant unmet need for pharmacotherapies addressing its core and associative symptoms. While some atypical antipsychotics have been approved for managing associated irritability and aggression, their use is constrained by substantial side effects. This study aimed firstly to develop behavioral measures to explore frustration, irritability and aggression phenotypes in the rat prenatal valproic acid (VPA) model of ASD. Additionally, we investigated the potential of two novel mechanisms, 5-HT_1B and TAAR1 agonism, to alleviate these behaviors. Male offspring exposed to prenatal VPA were trained to achieve stable performance on a cued operant task, followed by pharmacological assessment in an operant frustration test, bottle brush test and resident intruder test. VPA exposed rats demonstrated behaviors indicative of frustration and irritability, as well as increased aggression compared to controls. The irritability-like behavior and aggression were further exacerbated in animals previously experiencing a frustrative event during the operant test. Single administration of the 5-HT_1B agonist CP-94253 or TAAR1 agonist RO5263397 attenuated the frustration-like behavior compared to vehicle. Additionally, both agonists reduced irritability-like behavior under both normal and frustrative conditions. While CP-94253 reduced aggression in the resident intruder test under both conditions, RO5263397 only produced effects in rats that previously experienced a frustrative event. Our study describes previously uncharacterized phenotypes of frustration, irritability, and aggression in the rat prenatal VPA model of ASD. Administration of selective TAAR1 or 5-HT_1B receptor agonists alleviated these deficits, warranting further exploration of both targets in ASD treatment.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173862"},"PeriodicalIF":3.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cocaine diminishes consolidation of cued fear memory in female rats through interactions with ventral hippocampal D2 receptors","authors":"Daniela Gonzalez,&nbsp;Paige C. Bensing,&nbsp;Katherine N. Dixon,&nbsp;Kah-Chung Leong PhD","doi":"10.1016/j.pbb.2024.173863","DOIUrl":"10.1016/j.pbb.2024.173863","url":null,"abstract":"<div><p>In addition to cocaine's addictive properties, cocaine use may lead to heightened risk-taking behavior. The disruptive effects of cocaine on aversive memory formation may underlie this behavior. The present study investigated the effects of cocaine on fear memory using a cued fear conditioning paradigm in female Sprague Dawley rats, and further determined the role of D2 receptors in modulating the effect of cocaine on cued fear expression. Animals received six evenly spaced shocks preceded by a tone. The following day, rats were returned to the fear chamber where tones, but no shocks, were delivered. In Experiment 1, separate or concurrent administrations of cocaine (15 mg/kg; i.p.) and the D2 receptor antagonist eticlopride (0.1 mg/kg; i.p.) were given immediately after conditioning trials. It was determined that cocaine administration during the consolidation period diminished the expression of cued fear during the subsequent test day. Concurrent eticlopride administration attenuated this effect, indicating the involvement of D2 receptors in the deleterious effects of cocaine on fear memory consolidation. In Experiment 2, eticlopride (0.05 μg) was infused directly into the ventral hippocampus (VH) after fear conditioning and before cocaine administration. Cocaine continued to disrupt consolidation of cued and contextual fear memory, and concurrent intra-VH eticlopride blocked this effect, thereby demonstrating that VH D2 receptors mediate cocaine-induced impairment of fear memory consolidation. Overall, the present study provides evidence that acute cocaine administration impairs aversive memory formation and establishes a potential circuit through which cocaine induces its detrimental effects on fear memory consolidation.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"244 ","pages":"Article 173863"},"PeriodicalIF":3.3,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANXIOLYTICS: Origins, drug discovery, and mechanisms","authors":"Jeffrey M. Witkin ,&nbsp;James E. Barrett","doi":"10.1016/j.pbb.2024.173858","DOIUrl":"10.1016/j.pbb.2024.173858","url":null,"abstract":"<div><p>Anxiety is a part of the human condition and has been managed by psychoactive substances for centuries. The current medical need and societal demand for anxiolytic medicines has not abated. The present overview provides a brief historical introduction to the discovery of modern age anxiolytics that include the benzodiazepines together with a discussion of the continuing medical need for new antianxiety medications. The paper also discusses the use and impact of behavioral pharmacology in the preclinical development of anxiolytics. The review then highlights the diversity of mechanisms for creating a new generation of anxiolytics through mechanisms beyond the potentiation of GABA_A receptors and the blockade of monoamine uptake. A discussion then follows on the behavioral specificity of action of anxiolytics that includes the concept of creating an anxioselective drug, one that targets anxiety without producing untoward effects that include sedation and dependence. The use of anxiolytics in the treatment of other conditions such as substance use disorder is also briefly reviewed. Finally, a brief summary of the current status of anxiolytic drug development is provided. The review concludes with the idea that despite a host of anxiolytic drugs, the lack of efficacy in some patients and the side-effects and safety issues associated with some of these medications demands alternative medicines. Current preclinical and clinical research is ongoing with the goal of identifying such compounds.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173858"},"PeriodicalIF":3.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender differences in the relationship between nicotine exposure and symptoms of depression","authors":"Yalan Liu ,&nbsp;Li Zhang ,&nbsp;Shihao Fu ,&nbsp;Shengguo Wei ,&nbsp;Zhaofeng Jin ,&nbsp;Li He","doi":"10.1016/j.pbb.2024.173857","DOIUrl":"10.1016/j.pbb.2024.173857","url":null,"abstract":"<div><h3>Background</h3><p>Tobacco-derived nicotine exposure is linked to depression. However, the associations of nicotine and its metabolites with symptoms of depression, particularly concerning gender differences, remain underexplored.</p></div><div><h3>Methods</h3><p>The characteristics and total nicotine equivalents (TNE) of 1001 subjects were determined. The association between the TNE and symptoms of depression, accounting for gender differences, was investigated using generalized linear models and subgroup analyses.</p></div><div><h3>Results</h3><p>Men exhibited significantly greater levels of the nicotine exposure indicators TNE2, TNE3, TNE6, and TNE7 (<em>P</em> &lt; 0.005). A significantly greater percentage of women (23.45 %) than men (9.81 %) exhibited symptoms of depression (<em>P</em> &lt; 0.0001). In women, the relationship between the TNE and depression was reflected by a U-shaped curve with significant inflection points, particularly for TNE3, TNE6, and TNE7. Furthermore, in women, concentrations above 48.98 nmol/mL for TNE3, 53.70 nmol/mL for TNE6, and 57.54 nmol/mL for TNE7 were associated with 154 %, 145 %, and 138 % increases in the risk of depression, respectively. In contrast, these associations did not reach significance among men.</p></div><div><h3>Limitations</h3><p>The cross-sectional design limits the ability to infer causality between nicotine exposure and depressive symptoms. Larger-scale studies are needed to confirm these findings.</p></div><div><h3>Conclusions</h3><p>Gender could be a significant factor influencing the relationship between nicotine exposure levels and symptoms of depression. The impact of nicotine exposure on symptoms of depression should be particularly considered among women.</p></div><div><h3>Implications</h3><p>This study revealed the complex relationship between tobacco-related nicotine exposure and depressive symptoms, with a particular focus on gender differences. Our results revealed a distinct U-shaped correlation between total nicotine equivalents and depression in women, which differed from that in men. These findings emphasize the importance of tailoring clinical approaches to address nicotine exposure and manage depressive symptoms based on gender.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"244 ","pages":"Article 173857"},"PeriodicalIF":3.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower distress intolerance is associated with higher glutathione levels in adolescent cannabis users","authors":"Punitha Subramaniam ,&nbsp;Andrew Prescot ,&nbsp;James Yancey ,&nbsp;Erin McGlade ,&nbsp;Perry Renshaw ,&nbsp;Deborah Yurgelun-Todd","doi":"10.1016/j.pbb.2024.173861","DOIUrl":"10.1016/j.pbb.2024.173861","url":null,"abstract":"<div><p>Cannabis (CB) use and psychological stressors increase oxidative stress in the brain. Glutathione (GSH), the most abundant antioxidant in the brain, protects against oxidative stress. Furthermore, distress intolerance, the inability to tolerate psychological or physiological stress is a risk factor for CB use. The relationship between CB use, brain GSH levels and distress intolerance remains unknown. Therefore, we examined GSH levels in the anterior cingulate cortex (ACC), as a measure of oxidative stress, and its relationship with distress intolerance in adolescent CB users and healthy controls (HC).</p><p>Sixteen HC and 17 CB-using adolescents were included in the analysis. GSH levels were measured in the ACC using a metabolite-edited proton magnetic resonance spectroscopy sequence on a 3T scanner. Distress intolerance was assessed using the Distress Intolerance Index (DII) and CB use was evaluated using a structured clinical interview.</p><p>In the CB group, lower CSF-corrected GSH levels in the ACC were correlated with higher DII scores. However, no significant between group differences were observed for ACC CSF-corrected GSH levels or on DII scores. No significant correlations were observed in the HC group between GSH levels and DII.</p><p>Our findings suggests that the association between lower GSH levels and greater distress intolerance in CB users might reflect alterations in the balance between protective and oxidative stress conditions linked to the ability to tolerate distress. Further examination into this relationship can provide important insights into neurobiological correlates and risk factors associated with CB use to help inform preventive and treatment targets in the future.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173861"},"PeriodicalIF":3.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}