Journal of Psychopharmacology (Oxford, England)最新文献

{"title":"Transgenerational evidence of increases in dopamine D2 receptor sensitivity in rodents: Impact on sensorimotor gating, the behavioral response to nicotine and BDNF.","authors":"Wesley Drew Gill,&nbsp;Katherine C Burgess,&nbsp;Cynthia Vied,&nbsp;Russell W Brown","doi":"10.1177/02698811211033927","DOIUrl":"https://doi.org/10.1177/02698811211033927","url":null,"abstract":"<p><strong>Background/aims: </strong>Neonatal quinpirole (NQ) treatment to rats increases dopamine D₂ (DAD₂) receptor sensitivity in adult animals. We investigated if increased DAD₂ sensitivity would be passed to the next (F1) generation, and if these animals demonstrated sensorimotor gating deficits and enhanced behavioral responses to nicotine.</p><p><strong>Methods: </strong>Male and female rats were intraperitoneal (IP) administered quinpirole (1 mg/kg) or saline (NS) from postnatal day (P)1-21. Animals were either behaviorally tested (F0) or raised to P60 and mated, creating F1 offspring.</p><p><strong>Results: </strong>Experiment 1 revealed that F1 generation animals that were the offspring of at least one NQ-treated founder increased yawning behavior, a DAD₂-mediated behavioral event, in response to acute quinpirole (0.1 mg/kg). F1 generation rats also demonstrated increased striatal β arrestin-2 and decreased phospho-AKT signaling, consistent with increased G-protein independent DAD₂ signaling, which was equal to F0 NQ-treated founders, although this was not observed in all groups. RNA-Seq analysis revealed significant gene expression changes in the F1 generation that were offspring of both NQ-treated founders compared to F0 NQ founders and controls, with enrichment in sensitivity to stress hormones and cell signaling pathways. In Experiment 2, all F1 generation offspring demonstrated sensorimotor gating deficits compared to controls, which were equivalent to F0 NQ-treated founders. In Experiment 3, all F1 generation animals demonstrated enhanced nicotine behavioral sensitization and nucleus accumbens (NAcc) brain-derived neurotrophic factor (BDNF) protein. Further, F1 generation rats demonstrated enhanced adolescent nicotine conditioned place preference equivalent to NQ-treated founders conditioned with nicotine.</p><p><strong>Conclusions: </strong>This represents the first demonstration of transgenerational effects of increased DAD₂ sensitivity in a rodent model.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"1188-1203"},"PeriodicalIF":4.1,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/02698811211033927","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39207745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"5-HT_1B receptor agonist attenuates cocaine self-administration after protracted abstinence and relapse in rats.","authors":"Samantha N Scott,&nbsp;Raul Garcia,&nbsp;Gregory L Powell,&nbsp;Sophia M Doyle,&nbsp;Brielle Ruscitti,&nbsp;Tien Le,&nbsp;Aracely Esquer,&nbsp;Kevin M Blattner,&nbsp;Benjamin E Blass,&nbsp;Janet L Neisewander","doi":"10.1177/02698811211019279","DOIUrl":"https://doi.org/10.1177/02698811211019279","url":null,"abstract":"<p><strong>Background: </strong>The 5-HT_1B receptor (5-HT_1BR) agonist, CP94253, enhances cocaine intake during maintenance of self-administration (SA) but attenuates intake after 21 days of forced abstinence in male rats.</p><p><strong>Aims: </strong>We examined whether CP94253 attenuates cocaine intake in female rats after a period of abstinence, and if these attenuating effects persist or revert to enhancing cocaine intake during resumption (i.e. relapse) of daily cocaine SA.</p><p><strong>Methods: </strong>Male and female rats trained to lever press on a fixed ratio 5 schedule of cocaine reinforcement underwent ⩾21 days of forced abstinence. They were then tested for the effects of CP94253 (5.6 mg/kg, SC) or vehicle on cocaine SA. During the test session, rats had 1-h access to the training dose of cocaine (0.75 mg/kg, IV) followed by 1-h access to a lower cocaine dose (0.075 mg/kg, IV). Rats then resumed cocaine SA for 15 days to mimic relapse and were retested as done previously. Subsequently, rats underwent abstinence again (21-60 days) and were tested for CP94253 effects on locomotion and cue reactivity (i.e. responding for light/tone cues previously paired with cocaine infusions).</p><p><strong>Results: </strong>Regardless of sex, CP94253 decreased cocaine intake after abstinence and during resumption of SA and decreased cue reactivity while having no effect on locomotion.</p><p><strong>Conclusions: </strong>CP94253 decreases cocaine intake and cocaine seeking in both males and females even after resumption of cocaine SA. These findings suggest that the inhibitory effects of CP94253 observed after abstinence are long-lasting, and therefore, 5-HT_1BR agonists may have clinical efficacy as anti-relapse medications for cocaine use disorders.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"1216-1225"},"PeriodicalIF":4.1,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/02698811211019279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38948690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrasting effects of the α7 nicotinic receptor antagonist methyllycaconitine in different rat models of heroin reinstatement.","authors":"Josephine Palandri,&nbsp;Sharon L Smith,&nbsp;David J Heal,&nbsp;Sue Wonnacott,&nbsp;Chris P Bailey","doi":"10.1177/0269881121991570","DOIUrl":"https://doi.org/10.1177/0269881121991570","url":null,"abstract":"<p><strong>Background: </strong>α7 Nicotinic acetylcholine receptors are implicated in the reinstatement of drug-seeking, an important component of relapse. We showed previously that the α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, specifically attenuated morphine-primed reinstatement of conditioned place preference in rodents and this effect was mediated in the ventral hippocampus.</p><p><strong>Aims: </strong>The purpose of this study was to evaluate α7 nicotinic acetylcholine receptor antagonism in reinstatement of the conditioned place preference for the more widely abused opioid, heroin, and to compare the effect of α7 nicotinic acetylcholine receptor blockade on reinstatement of heroin-seeking and heroin self-administration in an intravenous self-administration model of addictive behaviour.</p><p><strong>Methods: </strong>Rats were trained to acquire heroin conditioned place preference or heroin self-administration; both followed by extinction of responding. Methyllycaconitine or saline was given prior to reinstatement of drug-primed conditioned place preference, or drug-prime plus cue-induced reinstatement of intravenous self-administration, using two protocols: without delivery of heroin in response to lever pressing to model heroin-seeking, or with heroin self-administration, using fixed and progressive ratio reward schedules, to model relapse.</p><p><strong>Results: </strong>Methyllycaconitine had no effect on acquisition of heroin conditioned place preference or lever-pressing for food rewards. Methyllycaconitine blocked reinstatement of heroin-primed conditioned place preference. Methyllycaconitine did not prevent drug-prime plus cue-induced reinstatement of heroin-seeking, reinstatement of heroin self-administration, or diminish the reinforcing effect of heroin.</p><p><strong>Conclusions: </strong>The α7 nicotinic acetylcholine receptor antagonist, methyllycaconitine, prevented reinstatement of the opioid conditioned place preference, consistent with a role for α7 nicotinic acetylcholine receptors in the retrieval of associative memories of drug liking. The lack of effect of methyllycaconitine in heroin-dependent rats in two intravenous self-administration models suggests that α7 nicotinic acetylcholine receptors do not play a role in later stages of heroin abuse.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"1204-1215"},"PeriodicalIF":4.1,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0269881121991570","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25454404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voluntary oral methamphetamine increases memory deficits and contextual sensitization during abstinence associated with decreased PKMζ and increased κOR in the hippocampus of female mice.","authors":"Jorge A Avila,&nbsp;Nicoletta Memos,&nbsp;Abdurrahman Aslan,&nbsp;Tytus Andrejewski,&nbsp;Victoria N Luine,&nbsp;Peter A Serrano","doi":"10.1177/02698811211048285","DOIUrl":"https://doi.org/10.1177/02698811211048285","url":null,"abstract":"<p><strong>Background: </strong>Female populations exhibit vulnerabilities to psychostimulant addiction, as well as cognitive dysfunction following bouts of abuse.</p><p><strong>Aims: </strong>The goal for this study was to advance our understanding of the mechanisms that produce sex disparities in drug addiction.</p><p><strong>Methods: </strong>We used an animal model for voluntary oral methamphetamine administration (VOMA) and focused on male and female mice that consumed 7.6-8.2 mg/kg of methamphetamine (MA) per day during the last 18 days of the paradigm.</p><p><strong>Results: </strong>The VOMA-exposed female mice displayed increased locomotor activity in the drug-administration context compared to male mice, demonstrating sex-specific changes in contextual sensitization. During 2 weeks of forced abstinence, mice underwent further behavioral testing. We show that abstinence increased open-arm entries on the elevated plus maze in both sexes. There were no differences in immobility on the tail suspension test. In a hippocampal-dependent radial arm maze task, VOMA-treated female mice, but not male mice, showed working memory deficits. Hippocampal tissue was collected and analyzed using Western blotting. VOMA-exposed female mice exhibited increased kappa opioid receptor (κOR) expression in the hippocampus compared to male mice, suggesting a vulnerability toward abstinence-induced dysphoria. Female VOMA mice also exhibited a decrease in the memory protein marker, protein kinase M zeta (PKMζ), in the hippocampus.</p><p><strong>Conclusions: </strong>Our study reveals sex-specific effects following abstinence from chronic MA consumption on hippocampal κOR and PKMζ expression, suggesting that these neural changes in female mice may underlie spatial memory deficits and identify an increased susceptibility to dysregulated neural mechanisms. These data validate VOMA as a model sensitive to sex differences in behavior and hippocampal neurochemistry following chronic MA exposure.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"1240-1252"},"PeriodicalIF":4.1,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083019/pdf/nihms-1798444.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39471257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoginkgetin treatment attenuated lipopolysaccharide-induced monoamine neurotransmitter deficiency and depression-like behaviors through downregulating p38/NF-κB signaling pathway and suppressing microglia-induced apoptosis.","authors":"Peng Li,&nbsp;Fucheng Zhang,&nbsp;Yajuan Li,&nbsp;Cai Zhang,&nbsp;Zhiyou Yang,&nbsp;Yongping Zhang,&nbsp;Cai Song","doi":"10.1177/02698811211032473","DOIUrl":"https://doi.org/10.1177/02698811211032473","url":null,"abstract":"<p><strong>Background: </strong>Microglia activation-induced neuroinflammation may contribute to the etiology of depression. <i>Podocarpus nagi</i> containing high concentration of isoginkgetin could effectively treat mental diseases in ancient times. However, the therapeutic role, peculiarly in the brain-immune modulation in depression is still unclear. This study aimed to determine effects of isoginkgetin on lipopolysaccharide (LPS)-induced depression-like changes. Furthermore, its modulation on the p38/nuclear factor-kappa B (NF-κB) pathway in LPS-activated microglia was evaluated.</p><p><strong>Methods: </strong>Adult Kunming mice were intraperitoneally injected vehicle or isoginkgetin (4 mg/kg) daily for 14 days before saline or LPS (0.83 mg/kg) administration. Depression-like behavior, neurotransmitter levels, and markers of neuroinflammation were determined. Isoginkgetin effect on LPS-induced microglial activation was then assessed in BV2 cells. Finally, conditioned medium (CM) derived from isoginkgetin-treated BV2 cells was co-cultured with SH-SY5Y cells for 24 h. Cell viability and apoptosis were evaluated.</p><p><strong>Results: </strong>LPS significantly induced helplessness and anxiety, which were associated with decreased 5-HT, noradrenaline, and dopamine concentrations. Meanwhile, LPS increased microglia M1 hallmark Iba1 expression and serum interleukin (IL)-1β concentration. These changes were attenuated by isoginkgetin treatment. In vitro, isoginkgetin markedly suppressed the production of IL-1β, IL-6, tumor necrosis factor-alpha, cyclooxygenase-2, inducible nitric oxide, and reactive oxygen species, which are released from LPS-stimulated BV2 cells. More interestingly, CM from isoginkgetin-treated BV2 cells significantly alleviated SH-SY5Y cell apoptosis and restored cell viability compared to LPS-treated group through the inhibition of p38/NF-κB signaling pathway.</p><p><strong>Conclusion: </strong>These data demonstrate that isoginkgetin is an effective therapeutic agent for depression-like behaviors and neuropathological changes via potent anti-inflammatory property.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"1285-1299"},"PeriodicalIF":4.1,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/02698811211032473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39199777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of the GluN2B subunit of glutamatergic NMDA receptors in rat brain areas after cocaine abstinence.","authors":"Irena Smaga,&nbsp;Karolina Wydra,&nbsp;Agata Suder,&nbsp;Marek Sanak,&nbsp;Lucia Caffino,&nbsp;Fabio Fumagalli,&nbsp;Małgorzata Filip","doi":"10.1177/02698811211048283","DOIUrl":"https://doi.org/10.1177/02698811211048283","url":null,"abstract":"Background: Cocaine use disorder is associated with compulsive drug-seeking and drug-taking, whereas relapse may be induced by several factors, including stress, drug-related places, people, and cues. Recent observations strongly support the involvement of the N-methyl-D-aspartate (NMDA) receptors in cocaine use disorders and abstinence, whereas withdrawal in different environments may affect the intensification of relapse. Methods: The aim of this study was to examine the GluN2B subunit expression and its association with the postsynaptic density protein 95 (PSD95) in several brain structures in rats with a history of cocaine self-administration and housed either in an enriched environment or in an isolated condition. Furthermore, a selective antagonist of the GluN2B subunit—CP 101,606 (10 and 20 mg/kg) administered during exposure to cocaine or a drug-associated conditional stimulus (a cue) was used to evaluate seeking behavior in rats. Results: In rats previously self-administering cocaine, we observed an increase in the GluN2B expression in the total homogenate from the dorsal hippocampus under both enriched environment and isolation. Cocaine abstinence under isolation conditions increased the GluN2B and GluN2B/PSD95 complex levels in the PSD fraction of the prelimbic cortex in rats previously self-administering cocaine. Administration of CP 101,606 attenuated cue-induced cocaine-seeking behavior only in isolation-housed rats. Conclusion: In summary, in this study we showed region-specific changes in both the expression of GluN2B subunit and NMDA receptor trafficking during cocaine abstinence under different housing conditions. Furthermore, we showed that the pharmacological blockade of the GluN2B subunit may be useful in attenuating cocaine-seeking behavior.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"1226-1239"},"PeriodicalIF":4.1,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39471258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational psychopharmacology.","authors":"Allan H Young","doi":"10.1177/02698811211053207","DOIUrl":"https://doi.org/10.1177/02698811211053207","url":null,"abstract":"The word ‘Translational’ is in great vogue in medical science at present. This is understandable as the key mission of medical science is to benefit humanity, and the translation of scientific advances into therapies is the foremost means by which this can be further enhanced. The fruits of this translational approach are now being harvested in many disease areas and there are great expectations that this will also happen in neurology and psychiatry. These hopes would seem well founded as psychopharmacology (at least in the modern era) has always been highly translational. This is especially true if we are clear that ‘Translation’ is a shuttle between basic studies and the clinic and back again. Indeed, much of the research upon which we base our understanding of brain function arose from work aimed at understanding the mechanism of action of serendipitously discovered treatments such as antipsychotics, antidepressants and so on. With this in mind, it is pleasing to observe that the papers published in this edition of the Journal show that Translational Psychopharmacology is itself in good health. Chellian and colleagues report an interesting review which investigates the benefits of using animal models to improve our understanding of the neuronal mechanisms underlying nicotine withdrawal associated with smoking cessation in humans. They suggest that research in animal modelling may lead to the development of novel pharmacotherapies for smoking cessation (Chellian et al., 2021). Also, highlighted in this review are age and sex differences in nicotine withdrawal symptoms found in animal studies. These findings may help the development of improved treatment strategies for smoking cessation. Gill and colleagues demonstrate the functional impact of increased dopamine D2 (DAD2) sensitivity in the next generation using neonatal quinpirole treatment to rats. Notably, this study shows that increases in DAD2 receptor sensitivity, which are common in psychosis, led to behavioural deficits in sensorimotor gating as well as increased behavioural responses to nicotine (Gill et al., 2021). Palandri and colleagues previously found that α7 Nicotinic acetylcholine receptors (nAChRs) antagonist, methyllycaconitine (MLA), specifically reduced morphine-primed reinstatement of conditioned place preference (CPP) in rodents, and this effect was mediated in the ventral hippocampus. Their present study aimed to evaluate α7 nAChR antagonism in reinstatement of CPP for the more widely abused opioid, heroin, comparing the effect of α7 nAChR blockade on reinstatement of heroinseeking and heroin self-administration in an intravenous selfadministration (IVSA) model of addictive behaviour. They report that the lack of effect of MLA in heroin-dependent rats in two IVSA models suggests that α7 nAChRs do not play a role in later stages of heroin abuse (Palandri et al., 2021). Scott and colleagues examined if pharmacological treatments may reduce the risk of relapse in patients suf","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"1167-1168"},"PeriodicalIF":4.1,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39530903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis.","authors":"Benjamin Jg Illingworth, Declan J Lewis, Andrew T Lambarth, Kate Stocking, James Mn Duffy, Luke A Jelen, James J Rucker","doi":"10.1177/0269881120965915","DOIUrl":"10.1177/0269881120965915","url":null,"abstract":"<p><strong>Rationale: </strong>Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials.</p><p><strong>Objective: </strong>To review the use of MDMA-assisted psychotherapy in treatment-resistant PTSD.</p><p><strong>Methods: </strong>Systematic searches of four databases were conducted from inception to February 2020. A meta-analysis was performed on trials which were double-blinded, randomised, and compared MDMA-assisted psychotherapy to psychotherapy and placebo. The primary outcomes were the differences in Clinician Administered PTSD Scale (CAPS-IV) score and Beck's Depression Inventory (BDI). Secondary outcome measures included neurocognitive and physical adverse effects, at the time, and within 7 days of intervention.</p><p><strong>Results: </strong>Four randomised controlled trials (RCTs) met inclusion criteria. When compared to active placebo, intervention groups taking 75 mg (MD -46.90; 95% (confidence intervals) CI -58.78, -35.02), 125 mg (MD -20.98; 95% CI -34.35, -7.61) but not 100 mg (MD -12.90; 95% CI -36.09, 10.29) of MDMA with psychotherapy, had significant decreases in CAPS-IV scores, as did the inactive placebo arm (MD -33.20; 95% CI -40.53, -25.87). A significant decrease in BDI when compared to active placebo (MD -10.80; 95% CI -20.39, -1.21) was only observed at 75 mg. Compared to placebo, participants reported significantly more episodes of low mood, nausea and jaw-clenching during sessions and lack of appetite after 7 days.</p><p><strong>Conclusion: </strong>These results demonstrate potential therapeutic benefit with minimal physical and neurocognitive risk for the use of MDMA-assisted psychotherapy in TR-PTSD, despite little effect on Beck's Depression Inventory. Better powered RCTs are required to investigate further.</p><p><strong>International prospective register of systematic reviews: </strong>CRD42019109132 available online at www.crd.york.ac.uk/prospero.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"501-511"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38735878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Projection-specific dopamine neurons in the ventral tegmental area participated in morphine-induced hyperalgesia and anti-nociceptive tolerance in male mice.","authors":"Guo-Lin Sun,&nbsp;Zhi-Jing Song,&nbsp;Xiao-Han Peng,&nbsp;Pan-Pan Chen,&nbsp;Ying Song,&nbsp;Xia Qin,&nbsp;Rong Hua,&nbsp;Yong-Mei Zhang","doi":"10.1177/0269881120985183","DOIUrl":"https://doi.org/10.1177/0269881120985183","url":null,"abstract":"<p><strong>Background: </strong>Long-term morphine use is associated with serious side effects, such as morphine-induced hyperalgesia and analgesic tolerance. Previous investigations have documented the association between dopamine (DA) neurons in the ventral tegmental area (VTA) and pain. However, whether VTA DA neurons are implicated in morphine-induced hyperalgesia and analgesic tolerance remains elusive.</p><p><strong>Methods: </strong>Initially, we observed behavioural effects of lidocaine administration into VTA or ablation of VTA DA neurons on morphine-induced hyperalgesia and anti-nociceptive tolerance. Subsequently, c-Fos expression in nucleus accumbens (NAc) shell-projecting and medial prefrontal cortex (mPFC)-projecting VTA DA neurons after chronic morphine treatment was respectively investigated. Afterwards, the effects of chemogenetic manipulation of NAc shell-projecting or mPFC-projecting DA neurons on morphine-induced hyperalgesia and anti-nociceptive tolerance were observed. Additionally, effects of chemogenetic manipulation of VTA GABA neurons on c-Fos expression in VTA DA neurons were investigated.</p><p><strong>Results: </strong>Lidocaine injection into VTA relieved established hyperalgesia and anti-nociceptive tolerance whereas ablation of VTA DA neurons prevented the development of morphine-induced hyperalgesia and anti-nociceptive tolerance. Chronic morphine treatment increased c-Fos expression in NAc shell-projecting DA neurons, rather than in mPFC-projecting DA neurons. Chemogenetic manipulation of NAc shell-projecting DA neurons had influence on morphine-induced hyperalgesia and tolerance. However, chemogenetic manipulation of mPFC-projecting DA neurons had no significant effects on morphine-induced hyperalgesia and anti-nociceptive tolerance. Chemogenetic manipulation of VTA GABA neurons affected the c-Fos expression in VTA DA neurons.</p><p><strong>Conclusions: </strong>These findings revealed the involvement of NAc shell-projecting VTA DA neurons in morphine-induced hyperalgesia and anti-nociceptive tolerance, and may shed new light on the clinical management of morphine-induced hyperalgesia and analgesic tolerance.</p><p><strong>Perspective: </strong>This study demonstrated that NAc shell-projecting DA neurons rather than mPFC-projecting DA neurons in the VTA were implicated in morphine-induced hyperalgesia and anti-nociceptive tolerance. Our findings may pave the way for the discovery of novel therapies for morphine-induced hyperalgesia and analgesic tolerance.</p>","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":" ","pages":"591-605"},"PeriodicalIF":4.1,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0269881120985183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25504385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated C-reactive protein among symptomatic youth with bipolar disorder","authors":"Yi Zou, Anahit Grigorian, S. Karthikeyan, B. Goldstein","doi":"10.1177/02698811221093796","DOIUrl":"https://doi.org/10.1177/02698811221093796","url":null,"abstract":"Rationale and Objectives: Increased levels of high-sensitivity C-reactive protein (CRP) are associated with mood symptoms in adults with bipolar disorder (BD). The few studies on this topic in youth with BD have not included controls. We, therefore, examined CRP levels in relation to symptomatic status in youth with and without BD. Methods: Participants included 154 youth (mean age 17 years; 48 asymptomatic BD, 39 symptomatic BD, 67 healthy controls (HC)). Rank analysis of covariance test examined group differences in CRP, controlling for age and sex. Correlation between CRP and mood symptom severity was examined using Spearman’s correlation within the BD group. Results: There were significant group differences in CRP levels (F(2,151) = 5.06, p = 0.007, η p 2 = 0 . 06 ); post hoc analyses showed higher CRP levels in the symptomatic BD group compared with HC (p = 0.01). In sensitivity analyses, this finding was no longer significant after controlling for body mass index (BMI). CRP was not significantly associated with symptomatic severity. Conclusions: CRP levels are elevated among symptomatic youth with BD, partly related to BMI. As elevated BMI is associated with mood symptom burden, prospective studies are warranted to parse the associations among mood symptoms, BMI, and inflammation. Given the proportion of time that youth with BD are symptomatic, present findings raise concern about the long-term impact of elevated CRP on blood vessels, brain, and related clinical outcomes.","PeriodicalId":156490,"journal":{"name":"Journal of Psychopharmacology (Oxford, England)","volume":"105 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129136861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}