The rodent electronic nicotine delivery system: Apparatus for voluntary nose‐only e‐cigarette aerosol inhalation

Journal of the Experimental Analysis of Behavior, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Tobacco use is the leading cause of death globally and in United States. After decades decline, driven by decreases combusted tobacco use, nicotine product has increased due to electronic delivery systems, also known as e-cigarettes or vapes. Preclinical models self-administration can serve important lodestars search for effective intervention prevention tactics. Current variants preclinical have substantial limitations, however. Therefore, we created rodent system (RENDS), a novel low-cost nonproprietary nose-only model aerosol self-administration. We confirmed that RENDS sequesters nose port measuring fine particulate matter (PM <2.5 microns) generated e-cigarettes. showed rats robustly self-administer flavored aerosol, resulting high blood levels cotinine (the major metabolite) spontaneous somatic withdrawal symptoms. Thus, provide validation operation function RENDS, opening door an open-source relatively low cost. Four existing operant chambers be retrofitted with less than $325/chamber. All diagrams plans custom-designed components are on Open Science Framework (https://osf.io/x2pqf/?view_only=775b55435b8e428f98e6da384ef7889d).

Language: Английский

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Expecting medication misuse: a proactive approach to drug discovery to prevent fatal overdose

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: March 17, 2025

Misuse of central nervous system (CNS) depressants (alprazolam, fentanyl, etc.) is a major cause fatal overdose, with high prevalence deaths involving polydrug interactions from the victim's own prescriptions. Thus, there an urgent need to improve safety CNS prevent fatalities. Pharmacological pursuits aiming harm through design non-addictive alternatives have either failed before clinical trials or produced mediocre treatment alternatives. Therefore, we propose new perspective for medicinal chemists: rather than misuse, must under expectation misuse. By shifting focus partial modulators full agonists, can develop novel chemical entities (NCEs) that intrinsically minimize physical caused by misuse without sacrificing therapeutic efficacy. In this perspective, provide overview two most widely misused classes medications (opioid and GABAA receptor modulators) in relation pharmacodynamic properties outcomes. We then suggest drug discovery pathway focused on physiological parameters. It our opinion approach would dramatically decrease lethality overdose outcomes treatments pain, anxiety, withdrawal alcohol, benzodiazepines, opioids.

Language: Английский

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The neuroplastic brain: current breakthroughs and emerging frontiers

Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 149643 - 149643

Published: April 1, 2025

Language: Английский

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Addictive behaviors: decades of research, but still so many questions!

Frontiers in Psychology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 6, 2024

Dominated by a 'market capitalism', i.e., an economic model promoting the buying and selling of goods services, we nowadays live in competitive, stressfull mass consumption society, where people increasingly exhibit behaviours aimed at satisfying personal material desires (Perez Esposito, 2010). Throughout their life, many will engage 'excessive acts', but only some them move towards unrestrictive, unrestrained, uncontrolled, maladaptive, addictive, behaviors.. Repeating activity despite explicitly stated desire to stop it due its harmful individual social consequences is hallmark addictive behavior (Santangelo et al., 2022). Decades research have tried understand which mechanisms trigger onset as well long-term maintenance such behaviors. Why how can arbitrary activity, clothes, eating food, watching TV series, drinking alcohol or gambling on sport events, become so central person compulsive that overtake all other activities? Classic addictions drugs substances may be understood means reinforcing properties specific brain networks. Indeed, various molecular targets, (such alcohol, cocaine, heroin, tobacco) act, increasing dopamine level, common biological pathway, mesolimbic circuit, more precisely, nucleus accumbens ventral striatum, resulting interoceptive feeling pleasure (reward) (Di Chiara Imperato, 1988). Repeated exposure substance promote encoding rewarding this event, acting therefore reinforcement learning signal, incentive salience reward stimulating motor action (Berridge Robinson, 1998). Transition from 'simple impulses consume' 'compulsive behaviors' appears linked dysfunctional (pre)frontal control system, implicated future-oriented processes regulating current actions relation goal-directed motivations (Robinson Berridge, 2003). Overall, substance-related seen reinforced-learned automatic response (a habit) highly salient resisting devaluation goal-inappropriateness (see Luscher 2020 for review). Nowadays, behind habits are learned operate remain topic ongoing research, with controversies regarding exact contribution (overestimated) habitual versus (underestimated) contextual maladaptive behaviors (Bouton, 2021; Buabang 2021). Also, if clearly imagine those substances, neurotoxic agents kill neurons (Singh Verma, 2020), could impact systems – contributing hypo-activity regions frontal cortex - situation even less clear when consider non-substance-related absence any ingestion agent, playing video games, gambling, media use 'addictive', represent (mainly among youths) significant public health concern? Of course, these "rewarding", also creating through system cues hijacking attention (Vidal Meshi, 2023). But explain transition compulsion effect? Several explicative "individual risk factors" development adolescence adulthood been proposed, motives (social, pleasure, coping…), family history (genetic part education), associated conduct disorders, inter-individual differences cognitive emotional regulation skills, personality traits (impulsivity, sensation seeking, taking…) gender (Petit 2013). Some evidence points implicit cognitions, unconscious associations memory ("When I feel bad, drink, better"), why they know being life threatening (Stacy Wiers, 2010 Altogether, makes story particularly complex, and, decades still triggers questions than responses. Addictive related not present strong neurobiological link (Grant 2006), patterns (Dubuson Given high co-occurrence (Burleigh 2019) rise polydrug (Crummy further needed improving understanding triggering (maybe translational going animal human research), prevention treatment strategies. Prevention difficult achieve, as, huge number potential contributive factors, impossible give recipe apply. Studies help define profiles high-risk developing highest importance fundamental clinical levels, moreover, aware conventional proposed treatments (based detoxification, psychotherapy anti-craving medication), modest. Aggregate disorder (SUD) remission (abstinence) rates were 10–15% given year (Fleury 2016), pointing urgent need find complementary effective add-on tools, globally enhance quality care, reduce gap (only small proportion –around 10%- adults SUD seeks treatment) (Knopf, 2024). The last emergence forms tools. New dimensions psychological interventions tested, mindfulness (Korecki 2020); eye movement desensitization reprocessing (EMDR; Carletto 2018); behavioral therapy (CBT; Ray bias modification programs (CBM; Manning 2019); new technologies remote automated web-based smartphone-based apps (Ferreri 2018). Neurocognitive models described two opposite underlying : abnormal bottom-up (impulsive, limbic) generating attentional biases (increased specifically cues), "wanting" (craving, drink) approach tendency, cannot "regulated" weakened reflective/executive (control, prefrontal) inhibit tendencies (Wiers 2007). On basis, studies sought abstinence decreasing and/or inhibitory training (MacLean 2018; Verdejo-Garcia 2023), using neuromodulation tools TMS (Antonelli 2021) tDCS (Lupi 2017); combining Tools neurofeedback (Russo 2023) virtual reality (Tsamitros used purpose. Many focused assessing biomarkers, markers changes, predict correlate disease trajectories responses (Volkow 2015; Campanella 2020; Poireau Nevertheless, efforts, outcomes modest (e.g., Fascher This least suggests should try renew care (fostering instance longer lengths services; Beaulieu 2021), rely refined (promoting inclusion stress neurocognitive models; Noel important role played section Behaviors Frontiers Psychology provide platform sharing scientific theoretical empirical works highlighting behaviors, elucidating protective risky including methods experimental paradigms face Importantly, heterogeneous (sometimes) counter-intuitive data researchers obtained far stresses extreme complexity phenomenon. naturally push adopt integrative perspective, would involve, interdisciplinary approach, social, behavioral, neural, emotional, manifestations methodological parameters better approximate experience, order field improved understanding, prevention, diagnosis, (Diehl Corley

Language: Английский

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The role of reward in substance use disorders: Introduction to the special issue

Pharmacology Biochemistry and Behavior, Journal Year: 2024, Volume and Issue: 247, P. 173928 - 173928

Published: Nov. 28, 2024

Language: Английский

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