Psychopharmacology最新文献

{"title":"Relapse after intermittent access to cocaine: Discriminative cues more effectively trigger drug seeking than do conditioned cues.","authors":"Ndeye Aissatou Ndiaye, Sema Abu Shamleh, Domiziana Casale, Sol'Abraham Castaneda-Ouellet, Isabel Laplante, Mike J F Robinson, Anne-Noël Samaha","doi":"10.1007/s00213-024-06614-9","DOIUrl":"10.1007/s00213-024-06614-9","url":null,"abstract":"<p><strong>Rationale: </strong>When people with drug addiction encounter cues associated with drug use, this can trigger cravings and relapse. These cues can include conditioned stimuli (CSs) signaling drug delivery and discriminative stimuli (DSs) signaling drug availability. Compared to CS effects, DS effects are less explored in preclinical studies on cue-induced relapse.</p><p><strong>Objective: </strong>We compared CS and DS effects on reward seeking following abstinence from intermittent-access cocaine (or sucrose) self-administration.</p><p><strong>Methods: </strong>During 15-20 intermittent-access sessions, rats self-administered i.v. cocaine or sucrose pellets paired with a light-tone CS. Cocaine/sucrose was available for 5-min (signalled by a light; DS+) and unavailable for 25 min (signalled by different lighting conditions; DS-), and this cycled for 4 h/session. Following abstinence, we measured cocaine/sucrose seeking under extinction triggered by CS and DS presentation, and instrumental responding reinforced by these cues.</p><p><strong>Results: </strong>Across intermittent-access sessions, rats increased lever pressing for cocaine or sucrose during DS+ periods and decreased responding during DS- periods. On days 2 and 21 of abstinence, only presentation of the DS+ or DS+ and CS combined elicited increased cocaine/sucrose-seeking behaviour (i.e., increased active lever presses). Presenting the DS- alongside the DS+ suppressed the increased cocaine-seeking behaviour otherwise produced by the DS+ . Finally, on day 21 of abstinence, rats showed equivalent levels of lever pressing reinforced by the DS+ , CS and by the DS+ and CS combined, suggesting comparable conditioned reinforcing value.</p><p><strong>Conclusions: </strong>After intermittent self-administration, cocaine-associated DSs and CSs acquire similar conditioned reinforcing properties, but DSs more effectively trigger increases in drug seeking.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of exercise duration on toluene-induced locomotor sensitization in mice: a focus on the Renin Angiotensin System.","authors":"Itzell A Gallardo-Ortíz, Alain Oros-González, Gabriela Rodríguez-Manzo, René Garduño-Gutiérrez, Andrés Aragón-Martínez, Nayeli Páez-Martínez","doi":"10.1007/s00213-024-06626-5","DOIUrl":"10.1007/s00213-024-06626-5","url":null,"abstract":"<p><strong>Rationale: </strong>Exercise attenuates addictive behavior; however, little is known about the contribution of exercise duration to this positive effect. The Renin Angiotensin System (RAS) has been implicated both in addictive responses and in the beneficial effects of exercise; though, its role in the advantageous effects of exercise on toluene-induced addictive responses has not been explored.</p><p><strong>Objectives: </strong>To evaluate the impact of different exercise regimens in mitigating the expression of toluene-induced locomotor sensitization and to analyze changes in RAS elements' expression at the mesocorticolimbic system after repeated toluene exposure and following voluntary wheel running in toluene-sensitized animals.</p><p><strong>Methods: </strong>Toluene-induced addictive-like response was evaluated with a locomotor sensitization model in mice. Toluene-sensitized animals had access to running wheels 1, 2, 4 or 24 h/day for 4 weeks; thereafter, locomotor sensitization expression was evaluated after a toluene challenge. RAS elements (ACE and ACE2 enzymes; AT1, AT2 and Mas receptors) expression was determined by Western blot in the VTA, NAc and PFCx of toluene-sensitized mice with and without exercise.</p><p><strong>Results: </strong>Individual differences in toluene-induced locomotor sensitization development were observed. Access to wheel running 1 and 2 h/day reduced but 4 and 24 h/day completely blocked locomotor sensitization expression. Repeated toluene exposure changed RAS elements' expression in the VTA, NAc and PFCx, while exercise mainly modified ACE and AT1 in air-exposed and toluene-sensitized mice.</p><p><strong>Conclusions: </strong>Inhalant-exposed animals show different sensitization phenotypes. Exercise duration determined its efficacy to attenuate the addictive-like response. Toluene exposure and exercise each modified RAS, the latter also modifying toluene-induced changes.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute nicotine administration reduces the efficacy of punishment in curbing remifentanil consumption in a seeking-taking chain schedule of reinforcement.","authors":"Sarah C Honeycutt, David D Lichte, Elizabeth A Gilles-Thomas, Ashmita Mukherjee, Gregory C Loney","doi":"10.1007/s00213-024-06613-w","DOIUrl":"10.1007/s00213-024-06613-w","url":null,"abstract":"<p><strong>Rationale: </strong>Nicotine dependence is highly comorbid with opioid use disorders (OUDs). The use of nicotine-containing products increases the propensity to misuse prescription opioids and addressing both nicotine and opioid use simultaneously is more efficacious for treatment of OUDs than treating opioid use alone.</p><p><strong>Objectives: </strong>Given this extreme comorbidity, further elucidation of the effects of nicotine as a factor in promoting vulnerability to development of OUDs is needed. Here, we sought to further explore the effects of nicotine administration on operant self-administration of remifentanil (RMF), a fast-acting synthetic µ-opioid receptor agonist, using a heterogenous seeking-taking chain schedule of reinforcement in unpunished and punished conditions.</p><p><strong>Methods: </strong>Male and female rats received nicotine (0.4 mg/kg) or saline prior to operant self-administration sessions. These sessions consisted of pressing a 'seeking' lever to gain access to a 'taking' lever that could be pressed for delivery of 3.2 µg/kg RMF. After acquisition, continued drug seeking/taking was punished through contingent delivery of foot-shock.</p><p><strong>Results: </strong>Nicotine, relative to saline, increased RMF consumption. Furthermore, nicotine treatment resulted in significantly higher seeking responses and cycles completed, and this effect became more pronounced during punished sessions as nicotine-treated rats suppressed RMF seeking significantly less than controls. Nicotine treatment functionally reduced the efficacy of foot-shock punishment as a deterrent of opioid-seeking.</p><p><strong>Conclusions: </strong>Nicotine administration enhanced both appetitive and consummatory responding for RMF and engendered a punishment-insensitive phenotype for RMF that was less impacted by contingent administration of foot-shock punishment. These findings provide further support for the hypothesis that nicotine augments vulnerability for addiction-like behaviors for opioids.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinoic acid-mediated homeostatic plasticity in the nucleus accumbens core contributes to incubation of cocaine craving.","authors":"Amanda M Wunsch, Eun-Kyung Hwang, Jonathan R Funke, Raines Baker, Alana Moutier, Mike Milovanovic, Thomas A Green, Marina E Wolf","doi":"10.1007/s00213-024-06612-x","DOIUrl":"10.1007/s00213-024-06612-x","url":null,"abstract":"<p><strong>Rationale: </strong>Incubation of cocaine craving refers to the progressive intensification of cue-induced craving during abstinence from cocaine self-administration. We showed previously that homomeric GluA1 Ca²⁺-permeable AMPARs (CP-AMPAR) accumulate in excitatory synapses of nucleus accumbens core (NAcc) medium spiny neurons (MSN) after ∼1 month of abstinence and thereafter their activation is required for expression of incubation. Therefore, it is important to understand mechanisms underlying CP-AMPAR plasticity.</p><p><strong>Objectives: </strong>We hypothesize that CP-AMPAR upregulation represents a retinoic acid (RA)-dependent form of homeostatic plasticity, previously described in other brain regions, in which a reduction in neuronal activity disinhibits RA synthesis, leading to GluA1 translation and CP-AMPAR synaptic insertion. We tested this using viral vectors to bidirectionally manipulate RA signaling in NAcc during abstinence following extended-access cocaine self-administration.</p><p><strong>Results: </strong>We used shRNA targeted to the RA degradative enzyme Cyp26b1 to increase RA signaling. This treatment accelerated incubation; rats expressed incubation on abstinence day (AD) 15, when it is not yet detected in control rats. It also accelerated CP-AMPAR synaptic insertion measured with slice physiology. CP-AMPARs were detected in Cyp26b1 shRNA-expressing MSN, but not control MSN, on AD15-18. Next, we used shRNA targeted to the major RA synthetic enzyme Aldh1a1 to reduce RA signaling. In MSN expressing Aldh1a1 shRNA, synaptic CP-AMPARs were reduced in late withdrawal (AD42-60) compared to controls. However, we did not detect an effect of this manipulation on incubated cocaine seeking (AD40).</p><p><strong>Conclusions: </strong>These findings support the hypothesis that increased RA signaling during abstinence contributes to CP-AMPAR accumulation and incubation of cocaine craving.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ceftriaxone reverses diet-induced deficits in goal-directed control.","authors":"Benjamin-Israel Moke, Megan L Shipman, Simon Lui, Laura Corbit","doi":"10.1007/s00213-024-06621-w","DOIUrl":"10.1007/s00213-024-06621-w","url":null,"abstract":"<p><strong>Rationale: </strong>Obesity is associated with numerous health risks and ever-increasing rates are a significant global concern. However, despite weight loss attempts many people have difficulty maintaining weight loss. Previous studies in animals have shown that chronic access to an obesogenic diet can disrupt goal-directed behavior, impairing the ability of animals to flexibly adjust food-seeking behavior following changes in the value of earned outcomes. Changes in behavioral control have been linked to disruption of glutamate transmission in the dorsal medial striatum (DMS), a region critical for the acquisition and expression of goal-directed behavior.</p><p><strong>Objectives: </strong>The goal of this study was to test whether ceftriaxone, a beta-lactam antibiotic shown elsewhere to upregulate the expression of the glutamate transporter GLT-1, would improve goal-directed control following long-term exposure to an obesogenic diet.</p><p><strong>Methods: </strong>Male and female rats were given access to either standard chow or chow plus sweetened condensed milk (SCM) for 6 weeks. Access to SCM was ended and rats received daily injections of either ceftriaxone or saline for 6 days. Rats were then trained to press a lever to earn a novel food reward and, finally, were assessed for sensitivity to outcome devaluation. Histological analyses examined changes to GLT-1 protein levels and morphological changes to astrocytes, within the DMS.</p><p><strong>Results: </strong>We found that ceftriaxone robustly restored goal-directed behavior in animals following long-term exposure to SCM. While we did not observe changes in protein levels of GLT-1 in the DMS, we observed that SCM induced changes in the morphology of astrocytes in the DMS, and that ceftriaxone mitigated these changes.</p><p><strong>Conclusions: </strong>These results demonstrate that long-term access to a SCM diet impairs goal-directed behavior while also altering the morphology of astrocytes in the DMS. Furthermore, these results suggest that ceftriaxone administration can reverse the impairment of goal-directed behavior potentially through its actions on astrocytes in decision-making circuitry.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypocretin-1 receptor antagonism improves inhibitory control during the Go/No-Go task in highly motivated, impulsive male mice.","authors":"Jeremy Metha, Yijun Ji, Clemens Braun, Janet R Nicholson, Luis De Lecea, Carsten Murawski, Daniel Hoyer, Laura H Jacobson","doi":"10.1007/s00213-024-06628-3","DOIUrl":"10.1007/s00213-024-06628-3","url":null,"abstract":"<p><strong>Rationale: </strong>Motivation and inhibitory control are dominantly regulated by the dopaminergic (DA) and noradrenergic (NA) systems, respectively. Hypothalamic hypocretin (orexin) neurons provide afferent inputs to DA and NA nuclei and hypocretin-1 receptors (HcrtR1) are implicated in reward and addiction. However, the role of the HcrtR1 in inhibitory control is not well understood.</p><p><strong>Objectives: </strong>To determine the effects of HcrtR1 antagonism and motivational state in inhibitory control using the go/no-go task in mice.</p><p><strong>Methods: </strong>n = 23 male C57Bl/6JArc mice were trained in a go/no-go task. Decision tree dendrogram analysis of training data identified more and less impulsive clusters of animals. A HcrtR1 antagonist (BI001, 12.5 mg/kg, per os) or vehicle were then administered 30 min before go/no-go testing, once daily for 5 days, under high (food-restricted) and low (free-feeding) motivational states in a latin-square crossover design. Compound exposure levels were assessed in a satellite group of animals.</p><p><strong>Results: </strong>HcrtR1 antagonism increased go accuracy and decreased no-go accuracy in free-feeding animals overall, whereas it decreased go accuracy and increased no-go accuracy only in more impulsive, food restricted mice. HcrtR1 antagonism also showed differential effects in premature responding, which was increased in response to the antagonist in free-feeding, less impulsive animals, and decreased in food restricted, more impulsive animals. HcrtR1 receptor occupancy by BI001 was estimated at ~ 66% during the task.</p><p><strong>Conclusions: </strong>These data indicate that hypocretin signalling plays roles in goal-directed behaviour and inhibitory control in a motivational state-dependant manner. While likely not useful in all settings, HcrtR1 antagonism may be beneficial in improving inhibitory control in impulsive subpopulations.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BNST CRF receptor type 1 modulates mechanical hypersensitivity induced by adolescent alcohol exposure in adult female mice.","authors":"Natalia B Bertagna, Eleanor B Holmgren, Sheila A Engi, Linh Ha, Fabio C Cruz, Lucas Albrechet-Souza, Tiffany A Wills","doi":"10.1007/s00213-024-06693-8","DOIUrl":"https://doi.org/10.1007/s00213-024-06693-8","url":null,"abstract":"<p><strong>Rationale: </strong>Alcohol exposure during adolescence has been linked to long-lasting behavioral consequences, contributing to the development of alcohol use disorder. Negative affect and chronic pain during alcohol withdrawal are critical factors influencing problematic alcohol use and relapse. Our previous research demonstrated that adolescent intermittent ethanol (AIE) vapor exposure elicits sex-specific negative affect-like behavior in adult mice following stress exposure. Additionally, AIE induces persistent mechanical hypersensitivity, which is accompanied by increased activation of corticotropin-releasing factor receptor type 1 (CRFR1) neurons in the dorsolateral bed nucleus of the stria terminalis (dlBNST).</p><p><strong>Objectives: </strong>This study extends previous work by investigating plasma corticosterone levels and CRFR1 protein expression in the dlBNST following restraint stress exposure in adult mice with an AIE history. We also aim to explore the role of dlBNST CRFR1 signaling in mediating negative affect-like behavior and mechanical hypersensitivity.</p><p><strong>Results: </strong>Female mice exhibited elevated plasma corticosterone levels compared to males following restraint stress. Moreover, females with AIE history showed higher expression of CRFR1 protein in the dlBNST compared to air controls. Antagonism of CRFR1 in the dlBNST blocked AIE-induced mechanical hypersensitivity in adult females but did not affect stress-induced negative affect-like behavior. In alcohol-naïve females, intra-dlBNST administration of a CRFR1 agonist induced mechanical hypersensitivity.</p><p><strong>Conclusions: </strong>These findings provide new insights into the neurobiological mechanisms underlying stress-induced negative affect and pain-related behavior, both influenced by a history of adolescent alcohol exposure. The results suggest that CRFR1 antagonists warrant further investigation for their potential in addressing alcohol-related chronic pain.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice.","authors":"Kelly K Wingfield, Teodora Misic, Kaahini Jain, Carly S McDermott, Nalia M Abney, Kayla T Richardson, Mia B Rubman, Jacob A Beierle, Sophia A Miracle, Emma J Sandago, Britahny M Baskin, William B Lynch, Kristyn N Borrelli, Emily J Yao, Elisha M Wachman, Camron D Bryant","doi":"10.1007/s00213-024-06694-7","DOIUrl":"10.1007/s00213-024-06694-7","url":null,"abstract":"<p><strong>Rationale: </strong>Opioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome (NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest during spontaneous withdrawal. Variability in NOWS severity necessitates a more individualized treatment approach. Ultrasonic vocalizations (USVs) in neonatal mice are emitted in isolation as a stress response and are increased during opioid withdrawal, thus modeling a negative affective state that can be utilized to test new treatments.</p><p><strong>Objectives: </strong>We sought to identify the behavioral and USV profile, brainstem transcriptomic adaptations, and role of kappa opioid receptors in USVs during neonatal opioid withdrawal.</p><p><strong>Methods: </strong>We employed a third trimester-approximate opioid exposure model, where neonatal inbred FVB/NJ pups were injected twice-daily with morphine (10mg/kg, s.c.) or saline (0.9%, 20 ul/g, s.c.) from postnatal day(P) 1 to P14. This protocol induces reduced weight gain, hypothermia, thermal hyperalgesia, and increased USVs during spontaneous morphine withdrawal.</p><p><strong>Results: </strong>On P14, there were increased USV emissions and altered USV syllables during withdrawal, including an increase in Complex 3 syllables in FVB/NJ females (but not males). Brainstem bulk mRNA sequencing revealed an upregulation of the kappa opioid receptor (Oprk1), which contributes to withdrawal-induced dysphoria. The kappa opioid receptor (KOR) antagonist, nor-BNI (30 mg/kg, s.c.), significantly reduced USVs in FVB/NJ females, but not males during spontaneous morphine withdrawal. Furthermore, the KOR agonist, U50,488h (0.625 mg/kg, s.c.), was sufficient to increase USVs on P10 (both sexes) and P14 (females only) in FVB/NJ mice.</p><p><strong>Conclusions: </strong>We identified an elevated USV syllable, Complex 3, and a female-specific recruitment of the dynorphin/KOR system in increased USVs associated with neonatal opioid withdrawal severity.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pituitary adenylate cyclase-activating polypeptide (PACAP)⁺ cells in the paraventricular nucleus of the thalamus: relationship with binge-type eating in male and female mice.","authors":"Genevieve R Curtis, Brody A Carpenter, Breanne E Pirino, Annie Hawks, George Li, Jessica R Barson","doi":"10.1007/s00213-024-06692-9","DOIUrl":"10.1007/s00213-024-06692-9","url":null,"abstract":"<p><strong>Rationale: </strong>Both the paraventricular nucleus of the thalamus (PVT) and the neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), are thought to be involved in food intake. Importantly, PACAP is expressed in cells of the PVT.</p><p><strong>Objectives: </strong>To determine if PACAP in cells of the PVT might mediate some of the involvement of the PVT with palatable food intake.</p><p><strong>Methods: </strong>In male and female C57BL/6 J mice and PACAP-Cre transgenic mice on a C57BL/6 J background, limited access to Milk Chocolate Ensure Plus® was used to establish a model of binge-type eating. Next, using quantitative real-time PCR, gene expression of PACAP in the PVT was measured in relation to this binge-type eating. Finally, using chemogenetics in PACAP-Cre transgenic mice, the effect of activation of PVT PACAP⁺ cells on binge-type eating was determined.</p><p><strong>Results: </strong>Males and females both engaged in binge-type eating with Ensure, although females engaged in this behavior to a greater degree than males. While females also had a higher baseline level of PVT PACAP mRNA than males, only males showed an increase in levels of PACAP after a history of exposure to Ensure, and only males showed a reduction in levels of PACAP immediately prior to a binge session. Conversely, activation of PACAP⁺ cells in the PVT reduced binge-type eating of Ensure, specifically in male mice.</p><p><strong>Conclusions: </strong>The present findings indicate that PVT PACAP⁺ cells influence and are influenced by binge-type eating. Thus, PACAP in the PVT might mediate some of the known involvement of the PVT with palatable food intake.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the reinforcing, antinociceptive, and respiratory depressant effects of prototypical and G-protein biased mu-opioid receptor agonists in male and female Sprague-Dawley rats.","authors":"C Austin Zamarripa, Tanya Pareek, Loc M Pham, Bruce E Blough, Hayley M Schrock, Eric J Vallender, Kenneth J Sufka, Kevin B Freeman","doi":"10.1007/s00213-024-06690-x","DOIUrl":"https://doi.org/10.1007/s00213-024-06690-x","url":null,"abstract":"<p><strong>Rationale: </strong>G-protein biased mu-opioid receptor (MOR) agonists have been reported to exhibit superior therapeutic windows compared to prototypical MOR agonists when relating antinociception to respiratory depression. However, there is relatively little research on the abuse potential of G-protein biased MOR agonists in relation to other behavioral endpoints.</p><p><strong>Objectives: </strong>The aim of the present study was to quantitatively compare the reinforcing, antinociceptive, and respiratory-depressant effects of the prototypical MOR agonists, fentanyl and oxycodone, to the G-protein biased MOR agonists, SR14968 and SR17018, in male and female rats.</p><p><strong>Methods: </strong>In the self-administration study, four separate groups of Sprague-Dawley (SD) rats self-administered intravenous (i.v.) fentanyl, oxycodone, SR14968, and SR17018 under a progressive-ratio schedule of reinforcement. Using a within-subjects design, separate cohorts of SD rats were tested with i.v. fentanyl, oxycodone, SR14968, and SR17018 using a hot-plate assay, assays of neuropathic and inflammatory antinociception, and whole-body plethysmography.</p><p><strong>Results: </strong>All MOR agonists functioned as reinforcers, but SR14968 and SR17018 were less efficacious relative to oxycodone and fentanyl. Moreover, all MOR agonists produced dose-dependent and fully efficacious antinociception across all nociception modalities. Oxycodone and fentanyl, but not SR14968 or SR17018, produced respiratory depression in a dose-dependent manner.</p><p><strong>Conclusion: </strong>The present results indicate that the G-protein biased MOR agonists tested herein produce MOR-typical antinociception, exhibit reduced but apparent abuse potential, and do not produce respiratory effects at doses that are above the antinociceptive range. Atypical MOR agonists within the SR series should be further studied as foundational molecules for the development of safter analgesics.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}