Addiction neuroscience最新文献

{"title":"Parvalbumin expression does not account for discrete electrophysiological profiles of glutamatergic ventral pallidal subpopulations","authors":"Robert D Graham ,&nbsp;Lisa Z Fang ,&nbsp;Jessica R Tooley ,&nbsp;Vani Kalyanaraman ,&nbsp;Mary Christine Stander ,&nbsp;Darshan Sapkota ,&nbsp;Michelle R Lynch ,&nbsp;Joseph D Dougherty ,&nbsp;Bryan A Copits ,&nbsp;Meaghan C Creed","doi":"10.1016/j.addicn.2024.100170","DOIUrl":"10.1016/j.addicn.2024.100170","url":null,"abstract":"<div><p>The ventral pallidum (VP) has emerged as a critical node in the mesolimbic reward system. Modulating the VP can impact the subjective valuation of rewards, reward motivation, and reward seeking under conflict, making it an attractive target for clinical neuromodulation therapies that manage substance use disorders. To understand how to rationally modulate the VP, we need a better understanding of the electrophysiological properties of VP neurons and the molecular and biophysical determinants of these properties. Here, we used patch-clamp electrophysiology to characterize the intrinsic properties of glutamatergic VP (VP_Glu) neurons and observed two distinct electrophysiological profiles: VP_Glu neurons that undergo depolarization block in response to progressively increasing current injection amplitudes and those that were resistant to depolarization block. To explore the mechanisms that could contribute to these distinct profiles, we used targeted ribosome affinity purification to identify ion channel subunits and regulatory proteins by isolating actively transcribed mRNA selectively from VP_Glu neurons. We then used this transcriptomic information to implement a Markov Chain Monte Carlo method to parameterize a large population of biophysically distinct multicompartment models of VP_Glu neurons conforming to either subpopulation. Based on prior literature suggesting parvalbumin (PV) is expressed in a subset of VP_Glu neurons, and that PV expression governs the firing properties of those neurons, we tested the hypothesis that PV expression accounted for differences in subgroups, by increasing the maximal firing frequency and conferring resistance to depolarization block. In contrast, our model determined that PV expression at physiological levels had no effect on maximum firing rate. However, supraphysiological expression levels of PV appeared to induce a depolarization block in previously depolarization block-resistant neuron models, suggesting that other intracellular calcium-binding proteins could play a role in determining the firing phenotype of VP_Glu neurons. We corroborated this result with single-cell patch-clamp RT-PCR, which confirmed that PV expression did not distinguish the two electrophysiologically distinct subpopulations. Together, these findings establish that VP_Glu neurons are composed of biophysically distinct subpopulations that have not been appreciated in prior studies interrogating the function of this population. With the advent of novel tools for cell-type specific pharmacology and targeted neurostimulation, this understanding will be critical for developing strategies to rationally modulate VP_Glu cells to treat disorders characterized by maladaptive reward seeking.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"12 ","pages":"Article 100170"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000294/pdfft?md5=87ebba1ea438c51ef905c3709974206e&pid=1-s2.0-S2772392524000294-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141952732","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":"A novel delta opioid receptor specific peptide reduces craving in an animal model of cocaine seeking","authors":"Pnina Shirel Itzhak-Israeli ,&nbsp;Hevroni Yael ,&nbsp;Erez Matsree ,&nbsp;Hilla Pe'er-Nissan ,&nbsp;Shira Ofer Lancman ,&nbsp;Barnea R ,&nbsp;Luboshits G ,&nbsp;Menachem Motiei ,&nbsp;Oshra Betzer ,&nbsp;Iris Gispan ,&nbsp;Rachela Popovtzer ,&nbsp;Yaakov Anker ,&nbsp;Firer MA ,&nbsp;Yadid G","doi":"10.1016/j.addicn.2024.100159","DOIUrl":"10.1016/j.addicn.2024.100159","url":null,"abstract":"<div><p>Substance use disorder, and particularly cocaine use disorder, is a complex disease that affects societal, economic, and psychological factors. Endogenous β-endorphin released after prolonged cocaine withdrawal has been reported to activate the accumbal delta-opioid receptor (DOR), leading to attenuated cocaine seeking<strong>.</strong> However, using DOR β-endorphin activation to treat cocaine use disorder is impractical since β-endorphin does not cross the blood-brain barrier. Also, only activation of the sub-group DOR1 efficiently attenuates craving, as activation of DOR2 yields an opposite effect. Here, we isolated a specific peptide, PEP1, from a phage display peptide library with similar biological properties to β–endorphin, demonstrating specificity for DOR1 and functioning as full receptor agonists. Our pharmacodynamic results showed fast trafficking incorporation of DOR into the cell membrane, interpreted as superior rehabilitation of the receptor and its bioavailability compared to commercial agonists. We administered PEP1, either intrabrain or intranasal, to rats trained to self-administer cocaine. PEP1 induced a significant decrease in cocaine-craving behavior and reinstatement in three different animal models of addiction. Also, PEP1 did not exhibit rewarding properties and did not interfere with the natural reward system. ICP-OES analysis revealed that at least one hour post-administration, PEP1 was retained in the brain rather than in peripheral organs. These findings render PEP1 a potential novel regulator of cocaine craving, especially for being non-addictive. Hence, PEP1 should be further examined as a possible new therapy for substance use disorder.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"12 ","pages":"Article 100159"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277239252400018X/pdfft?md5=fbfbeb1c1a2a28110f3d9f8557fee631&pid=1-s2.0-S277239252400018X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141408059","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":"Opioids, stress and addiction: From stress-induced analgesia to opioid heterodimers with extraordinary analgesic efficacy and without the side effects of traditional opioids","authors":"Giuseppe Cataldo ,&nbsp;Donald A. Simone ,&nbsp;Richard J Bodnar","doi":"10.1016/j.addicn.2024.100168","DOIUrl":"10.1016/j.addicn.2024.100168","url":null,"abstract":"<div><p>The Special Issue on Stress and Addiction is concerned with interrelationships between environmental stimuli such as stress and endogenous opioid systems that lead to addiction and other behaviors. Stress can have a profound effect on pain that is mediated in part through endogenous opioids. Here we briefly summarize investigation pertaining to the involvement of endogenous opioids in stress-induced analgesia, and their mediation by hypothalamo-pituitary-adrenal systems. Subsequent studies of the contribution of opioid receptor subtypes mediating supraspinal pain-inhibitory systems are examined using selective agonists and antagonists largely developed by Dr. Philip Portoghese. Because of the ongoing opioid epidemic yet the need to discover effective analgesics, we conclude with a discussion of several approaches to manage pain effectively without such serious side effects as tolerance and addiction, associated with traditional opioid use. These include opioid analgesic synergy, biased opioid agonism, and targeting of opioid receptor heteromers with bivalent ligands.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"12 ","pages":"Article 100168"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000270/pdfft?md5=a2d8f18b7836b6f645a2c2ae84ce1a6e&pid=1-s2.0-S2772392524000270-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141951253","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":"Stimulating the posterior parietal cortex reduces self-reported risk-taking propensity in people with tobacco use disorder","authors":"Francesca M. LoFaro ,&nbsp;Timothy Jordan ,&nbsp;Michael R. Apostol ,&nbsp;Vaughn R. Steele ,&nbsp;Anna B. Konova ,&nbsp;Nicole Petersen","doi":"10.1016/j.addicn.2024.100160","DOIUrl":"https://doi.org/10.1016/j.addicn.2024.100160","url":null,"abstract":"<div><p>Previous research has identified a replicable role for the posterior parietal cortex (PPC) in risk behaviors, but it is unclear whether this relationship is causal. Here, we used a targeted neuromodulation protocol leveraging a single-session of 10-Hz rTMS to the PPC versus a control region in the visual cortex (V5), as well as two active comparison regions [superior frontal gyrus (SFG), dorsolateral prefrontal cortex (DLPFC)] (within-person, randomized order), to examine within-session changes in a comprehensive measure of self-reported risk-taking propensity (the Domain-Specific Risk-Taking or DOSPERT scale). Individuals with tobacco use disorder were selected as sample participants who present with clinically relevant risk-taking propensity (<em>N</em> = 50; 14 women, mean [<em>SE</em>] age=33.1 [1.04] years). Results indicated that stimulating the PPC (versus V5) resulted in trend-level reductions in self-reported risk-taking propensity (region-by-time interaction, <em>P</em> = 0.065). A similar pattern emerged comparing PPC stimulation to effects of stimulating either the DLPFC (<em>P</em> = 0.080) or SFG (<em>P</em> = 0.032). PPC-related reductions in risk-taking propensity were domain general and potentially driven by changes in risk perception rather than perceptions of expected benefits of risk-taking. These findings support a possible causal role of the PPC in risk behaviors that warrants further consideration for therapeutic indications in conditions like tobacco use disorder.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"12 ","pages":"Article 100160"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000191/pdfft?md5=93a1e53929506642ab747d8a56d5c543&pid=1-s2.0-S2772392524000191-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141324730","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":"Dopamine D2 receptors in the bed nucleus of the stria terminalis modulate alcohol-related behaviors","authors":"Dipanwita Pati ,&nbsp;Lisa R. Taxier ,&nbsp;Mengfan Xia ,&nbsp;Sophia I. Lee ,&nbsp;Sara Y. Conley ,&nbsp;Tori Sides ,&nbsp;Kristen M. Boyt ,&nbsp;Avery C. Hunker ,&nbsp;Larry S. Zweifel ,&nbsp;Thomas L. Kash","doi":"10.1016/j.addicn.2024.100157","DOIUrl":"https://doi.org/10.1016/j.addicn.2024.100157","url":null,"abstract":"<div><p>Dysregulation of the dopamine (DA) system is a hallmark of substance use disorders, including alcohol use disorder (AUD). Of the DA receptor subtypes, the DA D2 receptors (D2Rs) play a key role in the reinforcing effects of alcohol. D2Rs are expressed in numerous brain regions associated with the regulation of appetitive behaviors. One such region is the bed nucleus of the stria terminalis (BNST), which has been linked to the development and maintenance of AUD. Recently, we identified alcohol withdrawal-related neuroadaptations in the periaqueductal gray/dorsal raphe to BNST DA circuit in male mice. However, the role of D2R-expressing BNST neurons in voluntary alcohol consumption is not well characterized. In this study, we used a CRISPR-Cas9-based viral approach, to selectively reduce the expression of D2Rs in BNST GABA neurons (BNST<em>^vgat Drd2</em>) and interrogated the impact on alcohol-related behaviors. In male mice, reduced BNST<em>^vgat Drd2</em> expression potentiated the stimulatory effects of alcohol and increased voluntary consumption of 20% w/v alcohol in a two-bottle choice intermittent access paradigm. This effect was not specific to alcohol, as BNST<em>^vgat Drd2</em> knockdown also increased sucrose intake in male mice. Interestingly, reduction in BNST<em>^vgat Drd2</em> expression in female mice did not alter alcohol-related behaviors but lowered the threshold for mechanical pain sensitivity. Collectively, our findings suggest a role for postsynaptic BNST D2Rs in the modulation of sex-specific behavioral responses to alcohol and sucrose.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"11 ","pages":"Article 100157"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000166/pdfft?md5=f500978a6abf3c8be8e031477e190553&pid=1-s2.0-S2772392524000166-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140918068","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":"Chst9 marks a spatially and transcriptionally unique population of Oprm1-expressing neurons in the nucleus accumbens","authors":"Emma Andraka,&nbsp;Robert A. Phillips III,&nbsp;Kasey L. Brida,&nbsp;Jeremy J. Day","doi":"10.1016/j.addicn.2024.100153","DOIUrl":"https://doi.org/10.1016/j.addicn.2024.100153","url":null,"abstract":"<div><p>Opioids produce addictive, analgesic, and euphoric effects via actions at mu opioid receptors (µORs). The µOR is encoded by the <em>Oprm1</em> gene and is expressed in multiple brain regions that regulate reward and motivation, such as the nucleus accumbens (NAc). <em>Oprm1</em> expression in NAc medium spiny neurons (MSNs) mediates opioid place preference, seeking, and consumption. However, recent single nucleus RNA sequencing (snRNA-seq) studies have revealed that multiple subpopulations of NAc neurons express <em>Oprm1</em> mRNA, making it unclear which populations mediate diverse behaviors resulting from µOR activation. Using published snRNA-seq datasets from the rat NAc, we identified a novel population of MSNs that express the highest levels of <em>Oprm1</em> of any NAc cell type. Here, we show that this population is selectively marked by expression of <em>Chst9</em>, a gene encoding a carbohydrate sulfotransferase. Notably, <em>Chst9</em>+ neurons exhibited more abundant expression of <em>Oprm1</em> as compared to other cell types, and formed discrete cellular clusters along the medial and ventral borders of the NAc shell subregion. Moreover, <em>CHST9</em> mRNA was also found to mark specific MSN populations in published human and primate snRNA-seq studies, indicating that this unique population may be conserved across species. Together, these results identify a spatially and transcriptionally distinct NAc neuron population characterized by the expression of <em>Chst9</em>. The abundant expression of <em>Oprm1</em> in this population and the conservation of these cells across species suggests that they may play a key functional role in opioid response and identify this subpopulation as a target for further investigation.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"11 ","pages":"Article 100153"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000129/pdfft?md5=fc7fad0705bc0f542ff4ad27f89f5fe5&pid=1-s2.0-S2772392524000129-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140641394","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":"Behavioral and neuronal extracellular vesicle biomarkers associated with nicotine's enhancement of the reinforcing strength of cocaine in female and male monkeys","authors":"Mia I. Allen ,&nbsp;Bernard N. Johnson ,&nbsp;Ashish Kumar ,&nbsp;Yixin Su ,&nbsp;Sangeeta Singh ,&nbsp;Gagan Deep ,&nbsp;Michael A. Nader","doi":"10.1016/j.addicn.2024.100151","DOIUrl":"10.1016/j.addicn.2024.100151","url":null,"abstract":"<div><p>While the majority of people with cocaine use disorders (CUD) also co-use tobacco/nicotine, most preclinical cocaine research does not include nicotine. The present study examined nicotine and cocaine co-use under several conditions of intravenous drug self-administration in monkeys, as well as potential peripheral biomarkers associated with co-use. In Experiment 1, male rhesus monkeys (<em>N</em> = 3) self-administered cocaine (0.001–0.1 mg/kg/injection) alone and with nicotine (0.01–0.03 mg/kg/injection) under a progressive-ratio schedule of reinforcement. When nicotine was added to cocaine, there was a significant leftward/upward shift in the number of injections received. In Experiment 2, socially housed female and male cynomolgus monkeys (<em>N</em> = 14) self-administered cocaine under a concurrent drug-vs-food choice schedule of reinforcement. Adding nicotine to the cocaine solution shifted the cocaine dose-response curves to the left, with more robust shifts noted in the female animals. There was no evidence of social rank differences. To assess reinforcing strength, delays were added to the presentation of drug; the co-use of nicotine and cocaine required significantly longer delays to decrease drug choice, compared with cocaine alone. Blood samples obtained post-session were used to analyze concentrations of neuronally derived small extracellular vesicles (NDE); significant differences in NDE profile were observed for kappa-opioid receptors when nicotine and cocaine were co-used compared with each drug alone and controls. These results suggest that drug interactions involving the co-use of nicotine and cocaine are not simply changing potency, but rather resulting in changes in reinforcing strength that should be utilized to better understand the neuropharmacology of CUD and the evaluation of potential treatments.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"11 ","pages":"Article 100151"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000105/pdfft?md5=9c05b54e7415daac669bd1a087eb1de7&pid=1-s2.0-S2772392524000105-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139889157","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":"Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to opioid antagonism","authors":"Madigan L. Bedard ,&nbsp;Xi-Ping Huang ,&nbsp;Jackson G. Murray ,&nbsp;Alexandra C. Nowlan ,&nbsp;Sara Y. Conley ,&nbsp;Sarah E. Mott ,&nbsp;Samuel J. Loyack ,&nbsp;Calista A. Cline ,&nbsp;Caroline G. Clodfelter ,&nbsp;Nabarun Dasgupta ,&nbsp;Brian Krumm ,&nbsp;Bryan L. Roth ,&nbsp;Zoe A. McElligott","doi":"10.1016/j.addicn.2024.100155","DOIUrl":"https://doi.org/10.1016/j.addicn.2024.100155","url":null,"abstract":"<div><p>Xylazine is in the unregulated drug supply at increasing rates, usually combined with fentanyl, necessitating understanding of its pharmacology. Despite commentary from politicians, and public health officials, it is unknown how xylazine impacts naloxone efficacy, and. few studies have examined it alone. Here, we examine the impact of xylazine alone and in combination with fentanyl on several behaviors in mice. Surprisingly, naloxone precipitates withdrawal from xylazine and fentanyl/xylazine coadministration, with enhanced sensitivity in females. Further, xylazine is a full agonist at kappa opioid receptors, a potential mechanism for its naloxone sensitivity. Finally, we demonstrate surprising effects of xylazine to kappa opioid antagonism, which are relevant for public health considerations. These data address an ongoing health crisis and will help inform critical policy and healthcare decisions.</p></div><div><h3>One-sentence summary</h3><p>We present surprising new insights into xylazine and fentanyl pharmacology with immediate implications for clinical practice and frontline public health.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"11 ","pages":"Article 100155"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000142/pdfft?md5=8decf75afaff283132157acacdcba54c&pid=1-s2.0-S2772392524000142-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140901948","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":"Adolescent nicotine exposure promotes adulthood opioid consumption that persists despite adverse consequences and increases the density of insular perineuronal nets","authors":"S.C. Honeycutt,&nbsp;A. Mukherjee,&nbsp;M.S. Paladino,&nbsp;E.A. Gilles-Thomas,&nbsp;G.C. Loney","doi":"10.1016/j.addicn.2024.100150","DOIUrl":"https://doi.org/10.1016/j.addicn.2024.100150","url":null,"abstract":"<div><p>Adolescence marks a sensitive period for neurodevelopment wherein exposure to drugs of abuse may disrupt maturation and induce persistent changes in neurophysiology which may exacerbate the risk for developing substance use disorders in adulthood. Adolescent nicotine exposure (ANE) enhances motivation to obtain drugs of abuse, particularly opioids, and increases vulnerability for the development of opioid use disorder (OUD). Here, we characterized ANE effects on learning about the adverse consequences of opioid consumption in adulthood in the absence of further nicotine administration. First, we show that ANE engenders punishment resistant fentanyl self-administration in a heterogenous seeking–taking chain schedule of reinforcement at least at the tested dose of fentanyl (0.75 µg/kg). We found that ANE rats consumed significantly more fentanyl and contingent foot shock punishment was less efficacious in limiting fentanyl seeking in ANE rats, relative to nicotine-naïve controls. Next, we demonstrated that ANE limits learning about the deleterious consequences of acute opioid intoxication in adulthood. In a combined conditioned taste avoidance and place preference paradigm we found that ANE resulted in significant reductions in the strength of morphine-induced CTA, and a simultaneous enhancement of CPP at a higher dose that was less capable of driving reinforcement in naïve controls. Finally, we examined the expression of perineuronal nets (PNNs) within insular cortex (IC) and found ANE rats to have increased density of PNNs across the anterior IC and significantly more parvalbumin-labeled IC cells relative to naïve controls. Together, these data lay the framework for a mechanistic explanation of the extreme comorbidity between nicotine use and development of OUDs.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"11 ","pages":"Article 100150"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000099/pdfft?md5=370611cdbfc92b44a00cc77fff0a6a5d&pid=1-s2.0-S2772392524000099-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139748337","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":"Examining a punishment-related brain circuit with miniature fluorescence microscopes and deep learning","authors":"Matthew C. Broomer ,&nbsp;Nicholas J. Beacher ,&nbsp;Michael W. Wang ,&nbsp;Da-Ting Lin","doi":"10.1016/j.addicn.2024.100154","DOIUrl":"https://doi.org/10.1016/j.addicn.2024.100154","url":null,"abstract":"<div><p>In humans experiencing substance use disorder (SUD), abstinence from drug use is often motivated by a desire to avoid some undesirable consequence of further use: health effects, legal ramifications, etc. This process can be experimentally modeled in rodents by training and subsequently punishing an operant response in a context-induced reinstatement procedure. Understanding the biobehavioral mechanisms underlying punishment learning is critical to understanding both abstinence and relapse in individuals with SUD. To date, most investigations into the neural mechanisms of context-induced reinstatement following punishment have utilized discrete loss-of-function manipulations that do not capture ongoing changes in neural circuitry related to punishment-induced behavior change. Here, we describe a two-pronged approach to analyzing the biobehavioral mechanisms of punishment learning using miniature fluorescence microscopes and deep learning algorithms. We review recent advancements in both techniques and consider a target neural circuit.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"11 ","pages":"Article 100154"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000130/pdfft?md5=abaf3128ebf1e2c3ad4d0bcd104cdbb4&pid=1-s2.0-S2772392524000130-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140605449","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}