Addiction neuroscience最新文献

{"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":"2024-06-05","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":"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":"2024-05-31","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":"The estrous cycle has no effect on incubation of methamphetamine craving and associated Fos expression in dorsomedial striatum and anterior intralaminar nucleus of thalamus","authors":"Hongyu Lin ,&nbsp;Adedayo Olaniran ,&nbsp;Sara Garmchi ,&nbsp;Julia Firlie ,&nbsp;Natalia Rincon ,&nbsp;Xuan Li","doi":"10.1016/j.addicn.2024.100158","DOIUrl":"10.1016/j.addicn.2024.100158","url":null,"abstract":"<div><p>Relapse is a major challenge in treating drug addiction, and drug seeking progressively increases after abstinence, a phenomenon termed “incubation of drug craving”. Previous studies demonstrated both sex differences and an effect of estrous cycle in female rats in incubation of cocaine craving. In contrast, while incubation of methamphetamine craving is similar across sexes, whether estrous cycle plays a role in this incubation has yet to be fully addressed. Moreover, whether neural mechanisms underlying incubation of methamphetamine craving differ across estrous cycles is largely unknown. To address these gaps, we first compared methamphetamine self-administration, and methamphetamine seeking on both abstinence days 1 and 28 between male rats and female rats across the estrous cycle. Next, we examined neuronal activation associated with incubated methamphetamine seeking in dorsomedial striatum (DMS) and lateral portion of the anterior intralaminar nucleus of thalamus (AIT-L), two brain areas previously implicated in incubation of methamphetamine craving. We found no effect of sex or estrous cycle on methamphetamine self-administration and methamphetamine seeking on abstinence days 1 and 28. We also found no effect of sex or estrous cycle on the number of Fos-expressing cells in DMS or AIT-L following methamphetamine seeking test. Taken together, our results showed that methamphetamine self-administration and incubation of methamphetamine craving was not dependent on sex or estrous cycles under our experimental condition, and the role of DMS and AIT-L in incubation of methamphetamine craving may be similar across sexes and across estrous cycles in female rats.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"11 ","pages":"Article 100158"},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000178/pdfft?md5=b425efde715176b156d81e3b1a4b212b&pid=1-s2.0-S2772392524000178-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141027990","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":"2024-05-08","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":"Mesocorticolimbic system reactivity to alcohol use-related visual cues as a function of alcohol sensitivity phenotype: A pilot fMRI study","authors":"Roberto U. Cofresí ,&nbsp;Spencer Upton ,&nbsp;Alexander A. Brown ,&nbsp;Thomas M. Piasecki ,&nbsp;Bruce D. Bartholow ,&nbsp;Brett Froeliger","doi":"10.1016/j.addicn.2024.100156","DOIUrl":"https://doi.org/10.1016/j.addicn.2024.100156","url":null,"abstract":"<div><p>Low sensitivity (LS) to alcohol is a risk factor for alcohol use disorder (AUD). Compared to peers with high sensitivity (HS), LS individuals drink more, report more problems, and exhibit potentiated alcohol cue reactivity (ACR). Heightened ACR suggests LS confers AUD risk <em>via</em> incentive sensitization, which is thought to take place in the mesocorticolimbic system. This study examined neural ACR in LS and HS individuals. Young adults (<em>N</em> = 32, <em>M</em>_age=20.3) were recruited based on the Alcohol Sensitivity Questionnaire (HS: <em>n</em> = 16; LS: <em>n</em> = 16; 9 females/group). Participants completed an event-related fMRI ACR task. Group LS had higher ACR in left ventrolateral prefrontal cortex than group HS. In group LS, ACR in left caudomedial orbitofrontal cortex or left putamen was low at low alcohol use levels and high at heavier or more problematic alcohol use levels, whereas the opposite was true in group HS. Alcohol use level also was associated with the level of ACR in left substantia nigra among males in group LS. Taken together, results suggest elevated mesocorticolimbic ACR among LS individuals, especially those using alcohol at hazardous levels. Future studies with larger samples are warranted to determine the neurobiological loci underlying LS-based amplified ACR and AUD risk.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"11 ","pages":"Article 100156"},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000154/pdfft?md5=4b144f2a3fc0dc0fbefe01cd30a54df1&pid=1-s2.0-S2772392524000154-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140906452","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":"2024-05-03","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":"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":"2024-04-18","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":"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":"2024-04-16","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}

{"title":"Addiction neurobiologists should study resilience","authors":"Alexandra Rogers,&nbsp;Frances Leslie","doi":"10.1016/j.addicn.2024.100152","DOIUrl":"10.1016/j.addicn.2024.100152","url":null,"abstract":"<div><p>The study of addiction has historically focused on identifying the differences which make susceptible individuals fall prey to drug use and abuse. This has resulted in a deep understanding of the learning, reward, and habit-formation circuits which drive initial drug reinforcement, as well as exploration of the cognitive control and anxiety systems which are important for craving and relapse to drug use. However, most human drug users and a smaller proportion of laboratory animals are resilient to addiction, meaning that they can use addictive drugs without developing substance use disorders. Evidence from the neurobiology of resilience in stress models suggests that the mechanisms of resilience are distinct from those of vulnerability, and thus may be missed if resilience is not investigated in a targeted manner. In this review, we briefly review the limitations in our knowledge which have resulted from a focus on addiction vulnerability. We next introduce the formal construct of resilience and its historical application in neurobiology and clinical research. Finally, we present evidence for the presence of resilience mechanisms in studies of addiction neuroscience and argue for an increase in the focused study of resilience to substance abuse. By intentionally identifying compensatory resilience mechanisms in addiction, rather than only focusing on mechanisms of susceptibility, more effective therapeutic approaches may be discovered.</p></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"11 ","pages":"Article 100152"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772392524000117/pdfft?md5=27564b800d2557bedb197a04b5c68f5d&pid=1-s2.0-S2772392524000117-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140086740","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":"2024-02-15","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}