Pharmacology Biochemistry and Behavior最新文献

{"title":"Sex differences in acute tolerance to the objective and subjective effects of alcohol","authors":"Annie K. Griffith,&nbsp;Mark T. Fillmore","doi":"10.1016/j.pbb.2025.174111","DOIUrl":"10.1016/j.pbb.2025.174111","url":null,"abstract":"<div><div>Alcohol is well known for impairing motor coordination and increasing subjective intoxication. Previous research has found that these effects are exacerbated in women, but such observations were limited to times when blood alcohol concentrations (BACs) were at or near peak. Interestingly, alcohol-induced impairment of motor coordination and subjective intoxication both demonstrate acute tolerance, meaning they recover faster than the decline of BAC as alcohol is eliminated. Consideration of acute tolerance to both measures in tandem is particularly important because if recovery from subjective intoxication outpaces recovery from objective motor impairment, a drinker may develop a false sense of freedom from the impairing effects of alcohol. Such a misjudgment can lead the drinker to engage in risky behavior as BAC declines. The present study examined whether sex differences were present in the acute tolerance to motor impairment and subjective intoxication. Twenty-five women and 25 men participated in a placebo-controlled study of their acute tolerance to motor impairment and subjective intoxication following a moderate dose of alcohol, 0.60 g/kg for women and 0.64 g/kg for men. Repeated assessments of motor coordination with a grooved pegboard and subjective intoxication with a visual analog scale were conducted seven times as BAC declined. While all participants demonstrated acute tolerance to both motor impairment and subjective intoxication, women exhibited significantly faster recovery from subjective intoxication than men. Consequently, women may be more likely than men to engage in risky behavior on the descending limb, such as alcohol-impaired driving.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174111"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258796","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":"Challenges in cross-test comparison of anxiety-related outcomes in rodents: A network meta-analysis","authors":"Didem Derici Yıldırım ,&nbsp;Özge Selin Çevik ,&nbsp;Erdal Horata ,&nbsp;Coşar Uzun","doi":"10.1016/j.pbb.2025.174116","DOIUrl":"10.1016/j.pbb.2025.174116","url":null,"abstract":"<div><div>Anxiety-like complex behavioral and psychological constructs are difficult to evaluate in rodents. Many studies have investigated which techniques are appropriate for measuring anxiety and related physiological parameters. Here, we used network meta-analysis to compare the current methods of assessing anxiety. We performed a comprehensive review and network meta-analysis by searching PubMed, EMBASE, the Cochrane Library, SCOPUS, and Web of Science for studies involving rodents with anxiety-related behaviors undergoing behavioral tests with certain keywords: The common parameters that emerged were total distance traveled, fecal boli count, and rearing behavior. In the 46 studies reviewed, the open-field test (OFT) and elevated plus maze (EPM) test appeared most often (in 45 and 43 studies, respectively), while the light–dark box (LDB) and elevated zero maze tests appeared less frequently (in two studies and one study, respectively Subsequently, the tests were ranked based on their likelihood of being the most effective measure for each outcome. For total distance traveled, the OFT showed a significant disadvantage over the EPM and LDB. For fecal boli, there was a significant difference between the LDB and OFT. There were no variations between tests in terms of rearing. Our findings reinforce the importance of considering each behavioral test's unique characteristics when selecting appropriate measures for anxiety-like behaviors. Researchers should exercise caution when interpreting single-measure outcomes and adopt a holistic approach that integrates multiple test results to achieve reliable and relevant conclusions. Network meta-analysis is a powerful tool for identifying the highlights, complexities, and inconsistencies of anxiety-related behaviors in rodents in preclinical anxiety models.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174116"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302625","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":"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":"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":"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":"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}