Pharmacology Biochemistry and Behavior最新文献

{"title":"Nicotine e-cigarette exposure in utero diminishes spatial memory and has negative effects on attention in a dose-, diet- and sex-dependent manner.","authors":"Nicole M. Roeder ,&nbsp;Samantha L. Penman ,&nbsp;Brittany J. Richardson ,&nbsp;Jia Wang ,&nbsp;Lily Freeman-Striegel ,&nbsp;Ojas Pareek ,&nbsp;Rina Eiden ,&nbsp;Saptarshi Chakraborty ,&nbsp;Panayotis K. Thanos","doi":"10.1016/j.pbb.2025.174102","DOIUrl":"10.1016/j.pbb.2025.174102","url":null,"abstract":"<div><h3>Rationale</h3><div>Clinical and preclinical literature has linked prenatal nicotine exposure to several cognitive effects, including memory and attentional deficits. However, many preclinical studies focus on effects during adulthood and do not use clinically relevant nicotine delivery system.</div></div><div><h3>Objective</h3><div>Our study aims to examine the impact of prenatal nicotine exposure on cognition in adolescents using an inhalation model to mimic e-cigarette exposure.</div></div><div><h3>Methods</h3><div>Pregnant rats were exposed to either air, 24 mg/mL nicotine (low-dose nicotine, LDNIC), or 59 mg/mL nicotine (high-dose nicotine, HDNIC). Inhalations were conducted daily from 0900 to 1100. Offspring from each of the treatment groups were provided with a normal diet (ND) or high-fat diet (HFD). Novel object recognition (NOR), Morris water maze (MWM), and object-based attention (OBA) testing were conducted during early (PND 24-30) and late-adolescent (PND 44-51) periods.</div></div><div><h3>Results</h3><div>NOR indicated that prenatal HDNIC rats spent significantly less time exploring objects compared to air controls. Altered exploratory behavior was also observed in OBA in a dose-dependent manner. HDNIC ND rats also displayed signs of memory deficit, and this was seen most robustly in HDNIC ND female rats, with no observed effects in the HFD group.</div></div><div><h3>Conclusions</h3><div>Overall, our study indicates that prenatal vaporized nicotine exposure negatively affects spatial memory and appears to diminish performance in attention-related tasks, while HFD seems to protect from these negative effects.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174102"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal LAG3 antibody infusion induces microglia-dependent antidepressant effect by mobilizing astrocytic P2Y1R-mediated BDNF synthesis in the hippocampus","authors":"Wenfeng Hu ,&nbsp;Minxiu Ye ,&nbsp;Qijun Dai ,&nbsp;Micona Sun ,&nbsp;Rongrong Song ,&nbsp;Xu Lu ,&nbsp;Chao Huang ,&nbsp;Lin Zhang ,&nbsp;Rongrong Yang","doi":"10.1016/j.pbb.2025.174114","DOIUrl":"10.1016/j.pbb.2025.174114","url":null,"abstract":"<div><div>Intranasal infusion of lymphocyte-activating gene-3 antibody (In-LAG3-Ab) has microglia-dependent antidepressant effects, but the underlying mechanism remains unclear. Since microglia can interact with astrocytes through purinergic signaling, we hypothesize that microglia-driven purinergic signaling may mediate the antidepressant effect of In-LAG3-Ab. The results showed that a single In-LAG3-Ab infusion in chronically stressed mice produced both an antidepressant effect and increased adenosine triphosphate (ATP) levels in the dentate gyrus, both of which were suppressed by chemogenetic inhibition of microglia in the dentate gyrus. Depletion of ATP or non-specific antagonism of purinergic receptors abolished the antidepressant effect of In-LAG3-Ab. Specific inhibition of purinergic 2Y1 receptors (P2Y1Rs), but not other purinergic receptors, in the hippocampus or conditional depletion of P2Y1Rs in astrocytes also abolished the antidepressant effect of In-LAG3-Ab. Brain-derived neurotrophic factor (BDNF) may act downstream of astrocytic P2Y1Rs to mediate the antidepressant effect of In-LAG3-Ab, as (i) chemogenetic inhibition of microglia in the dentate gyrus, specific deletion of astrocytic P2Y1Rs, and depletion of endogenous ATP abolished the reversal effect of In-LAG3-Ab on chronic stress-induced decreases in BDNF in the dentate gyrus, and (ii) infusion of BDNF-Ab into the hippocampus abolished the antidepressant effect of In-LAG3-Ab. These results suggest that astrocytic P2Y1R signaling associated with microglia stimulation may mediate the antidepressant effect of In-LAG3-Ab through BDNF.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174114"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Locomotor stimulant and drug discrimination effects of five synthetic cathinones in rodents","authors":"Michael B. Gatch,&nbsp;Rebecca Darbi Hill,&nbsp;Ritu A. Shetty,&nbsp;Nana Kofi Kusi-Boadum,&nbsp;Jeanne Priddy,&nbsp;Nathalie Sumien,&nbsp;Michael J. Forster","doi":"10.1016/j.pbb.2025.174100","DOIUrl":"10.1016/j.pbb.2025.174100","url":null,"abstract":"<div><div>Synthetic cathinones are synthesized as legal alternatives to methamphetamine, cocaine and MDMA, and can produce serious health risks. The DEA identified five synthetic cathinones of interest: N-ethylpentedrone, N-ethylheptedrone, N-butylhexedrone, 4-methylpentedrone, and 4-methyl-α-ethylaminopentiophenone (4-MEAP). These compounds were tested to determine their locomotor stimulant and psychostimulant-like discriminative stimulus effects. Locomotor activity was tested in male Swiss-Webster mice to identify behaviorally active dose ranges and time courses. Discriminative stimulus effects of the five synthetic cathinones were tested in male Sprague-Dawley rats trained to discriminate cocaine (10 mg/kg, 10-min pretreatment) or methamphetamine (1 mg/kg, 10-min pretreatment) from saline vehicle. Four of the test compounds produced locomotor stimulant effects comparable in efficacy to methamphetamine and cocaine, with rank order of potency: 4-MEAP &gt; N-ethylpentedrone &gt; N-ethylheptedrone &gt;4-methyl-pentedrone. N-butylhexedrone depressed locomotor activity. N-Ethylpentedrone and N-ethylheptedrone substituted for the discriminative stimulus effects produced by methamphetamine and cocaine. 4-MEAP fully substituted for methamphetamine. 4-Methylpentedrone fully substituted for cocaine, but only partially substituted for methamphetamine, while N-butylhexedrone partially substituted for cocaine in DD and failed to substitute for methamphetamine. Three of the compounds, N-ethylpentedrone, N-ethylheptedrone, and 4-MEAP produced robust psychostimulant-like effects, which suggests they will have abuse liability similar to cocaine or methamphetamine. 4-Methylpentedrone was a slow onset locomotor stimulant, and substituted for cocaine and only partially substituted for methamphetamine, which may indicate a weaker abuse liability compared to methamphetamine or cocaine. N-butylhexedrone produced weak psychostimulant-like effects, which suggests it may have limited use as a street drug on its own.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174100"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF2 modulates behavioral and hippocampal changes induced by chronic cocaine exposure during adolescence in mice","authors":"Sara Gil-Rodríguez ,&nbsp;Mario Berdugo-Gómez ,&nbsp;Silvia Claros ,&nbsp;Silvana-Yanina Romero-Zerbo ,&nbsp;M. Carmen Mañas-Padilla ,&nbsp;María del Carmen Gómez-Roldán ,&nbsp;Eduardo Blanco-Calvo ,&nbsp;María García-Fernández ,&nbsp;Luis J. Santín","doi":"10.1016/j.pbb.2025.174095","DOIUrl":"10.1016/j.pbb.2025.174095","url":null,"abstract":"<div><div>Adolescence is a period of heightened neuroplasticity and vulnerability to environmental insults, including drug exposure. In this study, we investigated the short- and long-term behavioral effects, as well as the long-term hippocampal effects, of chronic cocaine administration during adolescence, along with the potential neuroprotective role of insulin-like growth factor 2 (IGF2) in male C57BL/6J mice. Over 21 days, mice received daily intraperitoneal injections of saline, cocaine, IGF2, or a combination of cocaine and IGF2. Behavioral assessments were conducted immediately after treatment and following a 30-day abstinence period, using a battery of tests including marble burying, nest building, elevated plus maze, open field, novel place and object recognition, and forced swim. Cocaine-treated mice exhibited persistent compulsive-like behaviors and altered risk perception, effects that were attenuated by IGF2 co-administration. At the cellular level (after 40 days of abstinence), chronic cocaine reduced the density of parvalbumin-positive interneurons in the CA1 and CA3 hippocampal regions, an effect not mitigated by IGF2 co-administration. IGF2 treatment also increased expression of the presynaptic marker synaptotagmin, without altering postsynaptic proteins (PSD-95) or neurotrophic factors (BDNF, pro-BDNF). However, IGF2 downregulated IGF2R expression and impaired performance in hippocampus-dependent spatial memory, suggesting that receptor downregulation may underlie cognitive side effects. No significant differences were observed in markers of oxidative stress, neurogenesis, or basal corticosterone levels. These findings indicate that IGF2 partially counteracts behavioral and cellular alterations induced by adolescent cocaine exposure but may also impact specific cognitive domains. Overall, this study supports further investigation of IGF2 as a therapeutic strategy to mitigate long-term neurobehavioral consequences of adolescent drug use.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174095"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of sex, species, environmental context, and alternative reinforcers in animal models of cocaine use disorders","authors":"Mia I. Rough,&nbsp;Brianna F. Roberts,&nbsp;Michael A. Nader","doi":"10.1016/j.pbb.2025.174113","DOIUrl":"10.1016/j.pbb.2025.174113","url":null,"abstract":"<div><div>Cocaine use disorder (CUD) remains a major public health challenge with no effective pharmacological treatments to date. Although extensive preclinical research using animal models has advanced our understanding, these findings have yet to translate into clinical success. This review highlights key independent variables that should be incorporated to improve the validity and translational relevance of animal studies. The discussion is organized around three primary domains: the agent; the host; and the environment. Most studies in this review focus on cocaine as the agent and host factors such as species and sex are emphasized as important independent variables influencing outcomes. The central theme of this review is to emphasize, from a preclinical model perspective, the critical role of environmental context, including operant conditioning parameters like schedules of reinforcement and maintaining events, as well as social housing conditions, which profoundly impact cocaine-maintained behavior and the effectiveness of interventions for cocaine self-administration.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174113"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D1-like dopamine receptors in the dentate gyrus mediate cannabidiol's facilitation of extinction and prevention of reinstatement in methamphetamine-induced conditioned place preference","authors":"Elaheh Danesh ,&nbsp;Mohammad Saghafi ,&nbsp;Roghayeh Mozafari ,&nbsp;Somaye Mesgar ,&nbsp;Abbas Haghparast","doi":"10.1016/j.pbb.2025.174094","DOIUrl":"10.1016/j.pbb.2025.174094","url":null,"abstract":"<div><div>Methamphetamine (METH) is a highly addictive psychostimulant, and despite its widespread abuse, there are no FDA-approved treatments for METH use disorder (MUD). Cannabidiol (CBD), a non-psychoactive cannabinoid, has shown promise in reducing behaviors linked to psychostimulant use, including METH. However, the underlying neurobiological mechanisms remain unclear. Emerging evidence suggests that CBD may act on the dopamine system to influence drug-seeking behavior. D1-like dopamine receptors (D1Rs) in the hippocampus (HPC) are involved in memory processes related to rewards, which may contribute to CBD's effects. This study examined whether D1Rs in the dentate gyrus (DG) region of the HPC play a role in CBD's modulation of METH-induced conditioned place preference (CPP) during extinction and reinstatement. Adult male Wistar rats received the D1Rs antagonist SCH23390 (0.25, 1, and 4 μg/0.5 μl saline) into the DG region before intracerebroventricular injection of CBD (10 and 50 μg/5 μl of 12 % DMSO). Results show that the highest dose of SCH23390 (4 μg) significantly blocked CBD's ability to enhance extinction of METH-CPP. Moreover, SCH23390 (1 and 4 μg) reversed CBD's prevention of reinstatement of METH-CPP. These findings suggest that D1Rs in the DG region are involved in mediating CBD's effects and offer insights into its therapeutic potential for MUD.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"256 ","pages":"Article 174094"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomolecular correlates of incubated sucrose-seeking within ventromedial prefrontal cortex are sex- and subregion-selective","authors":"F.J. Cano,&nbsp;C.J.E. Denning,&nbsp;H. Udayashankar,&nbsp;S.D. Adler,&nbsp;K.E. Smith,&nbsp;V. Dang,&nbsp;K. Mohammadi,&nbsp;A.T. Reed Aparicio,&nbsp;A. Jotwani,&nbsp;L.L. Huerta Sanchez,&nbsp;K.K. Szumlinski","doi":"10.1016/j.pbb.2025.174088","DOIUrl":"10.1016/j.pbb.2025.174088","url":null,"abstract":"<div><div>The similar temporal profile of incubated food- vs. drug-craving has led to the hypothesis that these behavioral phenomena may involve common, time-dependent, biochemical adaptations within neural circuits governing motivated behavior. Previously, we reported that the mTOR inhibitor Everolimus dose-dependently blocks incubated cocaine-seeking and reverses incubation-related changes in mTOR activation in the prelimbic (PL) subregion of the prefrontal cortex (PFC). Herein, we examined the biomolecular correlates of incubated sucrose-craving within these PFC subregions. Female and male rats were trained to lever-press for 45 mg banana-flavored sucrose pellets, paired with a light + tone compound stimulus during daily 6-h sessions over 10 consecutive days. One or 30 days following the last operant-conditioning session, cue-reinforced responding was assessed. Rats of both sexes exhibited comparable incubated sucrose-craving, yet the majority of incubation-related protein changes were sex-specific. In males, incubated craving was associated with increased indices of Akt/mTOR activation in the IL, and increased mGlu5 dimer expression within both subregions, while females exhibited reduced indices of Akt and PKCε activation, as well as, mGlu5 monomer levels in the PL only. Systemic pretreatment with Everolimus (1.0 mg/kg) produced a modest effect on sucrose cue-reinforced responding that was sufficient to block the incubated response. Taken together, our immunoblotting and behavioral pharmacological data to date argue that different biomolecular mechanisms operate with the IL and PL to drive incubated cocaine- versus sucrose-craving, with mTOR playing a lesser role in the manifestation of incubated sucrose-craving.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"256 ","pages":"Article 174088"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Footshock stress enhances morphine-induced reward but attenuates aversion in behavior and neural mechanisms","authors":"Yi Chun Yu ,&nbsp;Anna Kozłowska ,&nbsp;Chi-Wen Wu ,&nbsp;Cai-N Cheng ,&nbsp;Yung-Chen Hsu ,&nbsp;Lu Lu Fang ,&nbsp;Andrew Chih Wei Huang","doi":"10.1016/j.pbb.2025.174092","DOIUrl":"10.1016/j.pbb.2025.174092","url":null,"abstract":"<div><div>The impact of stress on the behaviors and neural substrates underlying opioid use disorder (OUD) remains unclear. To investigate this, we employed a footshock treatment before the pre- and post-conditioning procedures for conditioned taste aversion (CTA) and conditioned place preference (CPP) with morphine injections. In the experiment, all rats were subjected to 10-second footshock (3 mA) or no footshock treatments. Subsequently, CTA was established by allowing all rats to drink a 0.1 % saccharin solution for 15 min before intraperitoneal injection with normal saline or 20 mg/kg of morphine. Aftre that, rats were placed in a CPP compartment for 30 min to induce CPP learning. The results showed that footshock enhanced freezing time during the situational reminder. Morphine simultaneously induced aversion in the CTA and reward in the CPP. Footshock stress attenuated morphine-induced aversion in the CTA and facilitated morphine-induced reward in the CPP task. c-Fos expression was downregulated in the basolateral amygdala (BLA) under morphine administration and upregulated in the PrL and IL under footshock stress. Combined footshock stress and morphine injections increased c-Fos expression in the prelimbic cortex (PrL), infralimbic cortex (IL), and BLA. Footshock stress appeared to disrupt the neural connectivities among the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), nucleus accumbens (NAc), and basolateral amygdala (BLA). The network data indicated that footshock stress facilitated addiction-related neural pathways for the NAc and the PrL, IL, and BLA after morphine administration. The findings extend the paradoxical hypothesis of abused drugs and provide clinical contributions to the literature on OUD.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"256 ","pages":"Article 174092"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Swiss-Webster and C57BL/6 mice are differentially sensitive to the stimulant effects of methamphetamine","authors":"Bo Jarrett Wood ,&nbsp;Nicole M. Hall ,&nbsp;M. Frances Vest ,&nbsp;Papori Sharma ,&nbsp;Kevin S. Murnane","doi":"10.1016/j.pbb.2025.174093","DOIUrl":"10.1016/j.pbb.2025.174093","url":null,"abstract":"<div><div>Methamphetamine is a highly addictive psychostimulant with significant neurobiological consequences, yet strain-dependent differences in its effects remain poorly understood. This study investigated behavioral and molecular differences in Swiss-Webster and C57BL/6 mice following methamphetamine exposure. Swiss-Webster mice exhibited greater behavioral sensitivity to methamphetamine compared to C57BL/6 mice, as demonstrated by lower peak doses required to elicit locomotor stimulation and conditioned place preference. Gene expression analyses revealed significantly higher striatal dopamine D2 receptor mRNA levels in Swiss-Webster mice, alongside a main effect of strain across multiple dopaminergic receptors, suggesting broader transcriptional differences may contribute to their heightened behavioral response. However, no strain differences were observed in dopamine transporter or dopamine D1 receptor mRNA expression. Following a neurotoxic binge-dosing regimen, both strains showed significant dopamine depletion, but no differences in the dopamine metabolite DOPAC were observed between strains in the striatum. Given the role of dopaminergic signaling in stimulant sensitivity and reward, these findings suggest that strain-dependent differences in methamphetamine response may reflect broader alterations in dopamine system function between these strains. This is the first study to directly compare Swiss-Webster and C57BL/6 mice in methamphetamine-induced CPP and provides novel insight into strain-specific drug reward mechanisms.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"256 ","pages":"Article 174093"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kisspeptin-13 induces hyperalgesia and modulates the expression of opioid and glutamate receptors in mice","authors":"Éva Bodnár,&nbsp;Katalin Eszter Ibos,&nbsp;Kata Filkor,&nbsp;Krisztina Csabafi","doi":"10.1016/j.pbb.2025.174098","DOIUrl":"10.1016/j.pbb.2025.174098","url":null,"abstract":"<div><div>Kisspeptins are hypothalamic neuropeptides well known for their role in reproductive biology. Our previous results have demonstrated that kisspeptin-13 (KP-13) has pronociceptive and anti-opioid effects. In our present experiments, we investigated the effects of KP-13 on nociception under both physiological and inflammatory conditions, as well as on the gene expression of regions involved in mediating pain sensation in C57BL/6 mice.</div><div>Different doses of KP-13 were administered to adult male C57BL/6 mice, and either the tail-flick latency was measured in the tail-flick test or the time spent with nocifensive behavior was determined in the formalin test. In another group of animals, after KP-13 treatment, qPCR was used to determine the relative gene expression of <em>Oprd1</em>, <em>Oprk1</em>, <em>Oprm1</em>, <em>Grin1</em>, <em>Grin2b</em>, <em>Grin2d</em>, and <em>Grm5</em> in samples of the dorsal root ganglion (DRG), amygdala, hypothalamus, and anterior cingulate cortex (ACC).</div><div>Our results showed that KP-13 treatment decreased the tail-flick latency in a dose-dependent manner. In the formalin test, the KP-13-treated group showed increased nocifensive behavior compared to the control group. In DRG, KP-13 caused upregulation of <em>Oprd1</em> and downregulation of <em>Oprk1</em>. In the amygdala, KP-13 decreased the expression of <em>Oprd1</em> and <em>Grin2b</em>. In the hypothalamus, both <em>Oprm1</em> and <em>Oprd1</em> were downregulated. In the ACC, <em>Oprk1</em> and <em>Grm5</em> expression increased, whereas a decrease in <em>Grin2b</em> expression was observed.</div><div>In conclusion, our results suggest that KP-13 has a hyperalgesic effect, which may be mediated by region-specific alterations in the gene expression of opioid and glutamate receptors.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"256 ","pages":"Article 174098"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}