Psychopharmacology最新文献

{"title":"Sex specific effects of ketamine, but not other glutamate receptor modulators, on ethanol self-administration and reinstatement of ethanol seeking in rats.","authors":"Megan L Bertholomey, Camryn Forbes, Bryan D McElroy, Mary M Torregrossa","doi":"10.1007/s00213-025-06782-2","DOIUrl":"10.1007/s00213-025-06782-2","url":null,"abstract":"<p><strong>Rationale: </strong>Alcohol use and major depressive disorder are frequently comorbid, with individuals diagnosed with a substance use disorder being nearly three times as likely to have major depression. Poor treatment responses are found for both disorders and are further complicated when they co-occur, underscoring the need for better therapies. One potential candidate is ketamine, which has been shown to have rapid and long-lasting effects in individuals with treatment-resistant depression and, in some studies, reduces drinking in alcohol use disorder. However, though women are more likely to have this comorbidity, few studies have examined sex-specific effects of ketamine on alcohol drinking, nor have studies assessed the potential for ketamine to reduce reinstatement of alcohol seeking.</p><p><strong>Objectives: </strong>The primary goal of the present studies was to determine the effects of ketamine on alcohol-motivated behaviors in male and female rats, including in a model of stress + cue-induced reinstatement of alcohol seeking using yohimbine (YOH).</p><p><strong>Results: </strong>We found a selective reduction in alcohol self-administration and YOH + cue-induced reinstatement in females, but not males at a dose of 10 mg/kg ketamine. However, the same dose of ketamine was effective in reducing YOH + cue-induced reinstatement of saccharin seeking in both sexes. In addition, a different NMDAR antagonist, memantine, was effective in reducing alcohol seeking in both sexes, while the ketamine metabolite hydroxynorketamine (HNK) had no effects.</p><p><strong>Conclusions: </strong>In summary, these data suggest that antagonism of NMDARs may be effective in reducing stress-related alcohol seeking, but that ketamine has unique properties that lead to female-specific effects on alcohol seeking.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2035-2045"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812135","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":"Assessment of abuse potential of furanylfentanyl and tetrahydrofuranylfentanyl.","authors":"Yuanyuan Chen, Miaojun Lai, Xiangyu Li, Yanling Qiao, Deli Xu, Dan Fu, Bin Di, Peng Xu","doi":"10.1007/s00213-025-06790-2","DOIUrl":"10.1007/s00213-025-06790-2","url":null,"abstract":"<p><strong>Rational: </strong>Furanylfentanyl and tetrahydrofuranylfentanyl (THF-F) have been emerging in numerous intoxication and overdose cases in recent years. However, there remains a data deficiency regarding the abuse potential of these novel fentanyl analogs.</p><p><strong>Objectives: </strong>This study was designed to systematically assess the abuse potential of furanylfentanyl and THF-F.</p><p><strong>Methods: </strong>In this study, we evaluated the abuse potential of furanylfentanyl and THF-F via the conditioned place preference (CPP), drug self-administration, drug discrimination, and naloxone-precipitated withdrawal experiments with fentanyl as a reference.</p><p><strong>Results: </strong>Results from CPP experiments indicated that furanylfentanyl and THF-F could induce CPP at minimum doses of 0.1 mg/kg and 3 mg/kg, respectively. These doses were 1 time and 30 times that of fentanyl (0.1 mg/kg). Furanylfentanyl elicited stable self-administration responses at 2.5 µg/kg/infusion, whereas THF-F did so at 50 µg/kg/infusion. In the drug-substitution test, furanylfentanyl and THF-F induced the maximum number of infusions at 1.10 µg/kg and 12.5 µg/kg, respectively, which were 1 time and 10 times that of fentanyl (1.21 µg/kg). In drug discrimination tests, all three substances were fully substituted for the discriminative-stimulus effects of heroin dose-dependently. The substitution potency of furanylfentanyl (ED₅₀ = 2.68 µg/kg) was similar to that of fentanyl (ED₅₀ = 2.66 µg/kg), while THF-F (ED₅₀ = 36.32 µg/kg) was 14-fold less potent than fentanyl. Repeated administration of furanylfentanyl and THF-F produced naloxone-precipitated withdrawal symptoms. Thus, furanylfentanyl exhibited comparable potency to fentanyl in terms of rewarding, reinforcing, and subjective effects, while THF-F had reduced potency in these effects. Both of them had physical dependence.</p><p><strong>Conclusions: </strong>Taken together, our study presented new evidence indicating that furanylfentanyl and THF-F exhibit significant abuse potential in rodent models, which provides experimental data for the control. Furthermore, our study offered valuable information for future studies into the addictive properties of structurally modified fentanyl analogs.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2123-2133"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977103","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":"Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1^{G93 A}) mouse model of amyotrophic lateral sclerosis.","authors":"Sandip Ghimire, Fabian Kreilaus, Rossana Rosa Porto, Lyndsey L Anderson, Justin J Yerbury, Jonathon C Arnold, Tim Karl","doi":"10.1007/s00213-025-06785-z","DOIUrl":"10.1007/s00213-025-06785-z","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting voluntary muscle movement as well as cognitive and other behavioural domains at later disease stages. No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the copper-zinc superoxide dismutase 1 (SOD1) mouse model of ALS that carries a G93A mutation (SOD1^G93A).</p><p><strong>Methods: </strong>Male and female SOD1^G93A and wild type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.</p><p><strong>Results: </strong>CBD treatment ameliorated the bodyweight loss in female SOD1^G93A mice, tended to reinstate sociability in SOD1^G93A males, strengthened social recognition memory in SOD1^G93A females, and improved the PPI response in younger SOD1^G93A females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male SOD1^G93A mice and decreased the acoustic startle response and strengthened cue freezing in male mice.</p><p><strong>Conclusion: </strong>Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of SOD1^G93A mice in a sex specific manner without altering the motor phenotype.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2077-2095"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051074","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":"A scoping review of the effects of serotonergic psychedelics on attitudes towards death.","authors":"Noah N T Barr, Kayla J Giese, Sam G Moreton","doi":"10.1007/s00213-025-06787-x","DOIUrl":"10.1007/s00213-025-06787-x","url":null,"abstract":"<p><strong>Rationale: </strong>Emerging evidence suggests that psychedelic experiences have the potential to change attitudes towards death and reduce death anxiety. Improved attitudes towards death, specifically reduced death anxiety, are of psychological significance for clinical and non-clinical populations alike. Despite this emerging evidence, little is known about the phenomenology of this potential outcome.</p><p><strong>Objectives: </strong>To provide a systematic overview of studies reporting effects of psychedelics on attitudes towards death and death anxiety, thereby identifying any gaps in the current literature and informing suggestions for future research.</p><p><strong>Methods: </strong>MEDLINE, Scopus, PsycINFO, and Web of Science were systematically searched for empirical studies that measured attitudes towards death and death anxiety as an outcomes of classical psychedelic use. There were no limits on the date or design of the study.</p><p><strong>Results: </strong>The thirty-one studies included in the review all reported changes in attitudes towards death and/or changes in death anxiety. Despite finding evidence for psychedelics improving death anxiety, we found significant gaps in the existing research relating to the role of set and setting, potential differences across substances, the underlying psychological mechanisms involved, the potential for worsening of death anxiety, and the role of expectancy and placebo effects.</p><p><strong>Conclusions: </strong>There is largely consistent evidence that psychedelics can often change attitudes towards death and reduce death anxiety. However, less is known about the reliability and strength of these effects, the conditions under which they are likely to emerge and aspects of the experience that best predict them.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1955-1976"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014471","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":"The effect of nicotine on threat avoidance behaviour in healthy non-smokers.","authors":"Madeleine Mueller, Christoph Korn, Jan Haaker","doi":"10.1007/s00213-025-06789-9","DOIUrl":"10.1007/s00213-025-06789-9","url":null,"abstract":"<p><strong>Rationale: </strong>Developing adaptive strategies for survival relies on distinguishing danger from safety through aversive learning mechanisms. Chronic and acute nicotine exposure have been linked to impaired aversive learning and reduced discrimination between threat and safety. Yet, it is unclear if nicotine also impacts one behavioural consequence of aversive learning, which is the avoidance of threats.</p><p><strong>Objectives: </strong>This preregistered study examines how acute nicotine influences costly avoidance behaviour in non-smokers.</p><p><strong>Methods: </strong>To this end, healthy non-smoking participants (n = 66) received either 1 mg nicotine or a placebo in a double-blind design and underwent an active avoidance task. During acquisition, participants could choose between a safer but longer path to reach their goal or a shorter path (less effort) with a higher chance of receiving an aversive outcome in the form of an electrical stimulus. During uninstructed extinction, both paths no longer contained the risk of an aversive outcome and participants could learn this new safety association by trial and error. Finally, an instructed extinction phase indicated complete safety.</p><p><strong>Results: </strong>Contrary to our pre-registered hypotheses, participants with nicotine intake showed a trendwise reduced avoidance of aversive outcomes, compared to placebo controls. Further analysis revealed however that nicotine did not enhance safety learning during extinction in the nicotine group, as compared to controls.</p><p><strong>Conclusions: </strong>In conclusion, this study strengthens the evidence that nicotine alters learning to identify threat and safety, which is also transferred to avoidance behaviour.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2111-2121"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042833","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":"Comment on the study \"the efficacy and safety of zuranolone for treatment of depression: a systematic review and meta-analysis\".","authors":"Mohammad Umer, Zaofasha Zaheer, Aiman Naveed","doi":"10.1007/s00213-025-06776-0","DOIUrl":"10.1007/s00213-025-06776-0","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2135-2138"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812134","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":"Decoding the genetic links between substance use disorder and cancer vulnerability.","authors":"Xin Su, Xiaoyan Mo, Jun Kan, Fan Yang, Bei Zhang, Yuanyuan Huang","doi":"10.1007/s00213-025-06781-3","DOIUrl":"10.1007/s00213-025-06781-3","url":null,"abstract":"<p><strong>Objective: </strong>Cancer remains a leading cause of mortality and morbidity worldwide, imposing a significant public health burden. While cannabis and opioids are widely used in cancer pain management, their potential for abuse and addiction has raised concerns regarding their long-term health effects, including possible associations with cancer risk. However, the relationship between substance use disorders (SUDs) and cancer susceptibility remains controversial. This Mendelian randomization (MR) study aimed to investigate the potential causal effects of cannabis use disorder (CUD) and opioids use disorder (OUD) on cancer vulnerability.</p><p><strong>Methods: </strong>We conducted a two-sample MR study using summary statistics from genome-wide association studies, including data from FinnGen and UK Biobank. The primary analytical approach was the inverse-variance weighted (IVW), complemented by a range of sensitivity analyses to assess the robustness of the findings.</p><p><strong>Results: </strong>IVW analysis identified a causal association between OUD and bladder cancer (OR = 1.040, 95% CI 1.004-1.078, P = 0.029, adj. P = 0.125), acute myeloid leukemia (OR = 0.931, 95% CI 0.885-0.978, P = 0.005, adj. P = 0.061) and ovarian cancer (OR = 0.937, 95% CI 0.891-0.984, P = 0.010, adj. P = 0.064). Sensitivity analysis yielded directionally consistent results. Reverse MR analysis provided no statistically significant evidence supporting a causal effect of these cancers on OUD (all P > 0.05). Additionally, no evidence of a significant causal relationship was observed between CUD and any cancer type (P > 0.05).</p><p><strong>Conclusions: </strong>This study suggests a potential causal link between OUD and increased susceptibility to bladder cancer, acute myeloid leukemia, and ovarian cancer, warranting further investigation in larger, multi-ethnic population studies. These results contribute to the ongoing discourse on the long-term health impacts of substance use disorders and highlight the need for further research to elucidate their potential oncogenic effects.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2021-2033"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773272","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":"Early oral administration of THC:CBD formulations prevent pain-related behaviors without exacerbating paclitaxel-induced changes in weight, locomotion, and anxiety in a rat model of chemotherapy-induced neuropathy.","authors":"Delia Soriano, Pablo Rodolfo Brumovsky, Marcelo José Villar, María Florencia Coronel","doi":"10.1007/s00213-025-06778-y","DOIUrl":"10.1007/s00213-025-06778-y","url":null,"abstract":"<p><strong>Rationale: </strong>Paclitaxel-induced neuropathy stands out as the primary, dose-limiting side effect of this extensively used chemotherapy agent. Prolonged hypersensitivity and pain represent the most severe clinical manifestations. Effective preventive and therapeutic strategies are currently lacking.</p><p><strong>Objectives: </strong>Our study aimed to assess the impact of early oral administration of pharmaceutical-grade formulations containing the phytocannabinoids THC and CBD in a rat model of paclitaxel-induced neuropathy.</p><p><strong>Methods: </strong>The experimental design involved the co-administration of paclitaxel and cannabinoid formulations with different THC to CBD ratios (THC:CBD 1:1 and THC:CBD 1:20) to adult male rats. Mechanical and thermal sensitivity, locomotor activity, vertical exploratory behaviors, anxiety-related parameters, weight gain, food and water consumption, and liver functionality were assessed.</p><p><strong>Results: </strong>Daily administration of THC:CBD 1:1 successfully prevented paclitaxel-induced cold allodynia, while THC:CBD 1:20 effectively prevented both thermal and mechanical hypersensitivities. Additionally, THC:CBD 1:1 formulation restored rearing behavior, significantly reduced by paclitaxel. Conversely, neither cannabinoid formulation was able to counteract paclitaxel-induced hypo-locomotion, reduced vertical exploratory activity, increased anxiety-like behaviors, attenuated weight gain, or decreased food and water intakes. However, the formulations employed did not induce further alterations or toxicity in animals receiving paclitaxel, and no signs of liver damage were detected.</p><p><strong>Conclusions: </strong>Our results suggest a differential therapeutic effect of two THC:CBD formulations on pain-related behaviors and spontaneous activities, particularly in the context of peripheral neuropathy. These formulations represent a promising therapeutic strategy not only to managing pain but also for enhancing daily activities and improving the quality of life for cancer patients.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1977-1994"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753435","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":"Quercetin ameliorates chronic restraint stress- and LPS-induced anxiety-like behaviors by modulating neuroinflammation in the lateral hypothalamus.","authors":"Xinxin Wang, Guangdong Weng, Yunpei Gao, Yu Wang, Chengxin Zhang","doi":"10.1007/s00213-025-06784-0","DOIUrl":"10.1007/s00213-025-06784-0","url":null,"abstract":"<p><strong>Objective: </strong>Quercetin is a natural flavonoid which has been shown to exhibit anti-inflammatory and anxiolytic properties. Neuroinflammation has recently been identified as a major cause of anxiety disorders. Both the lateral hypothalamus (LH) and bed nucleus of the stria terminalis (BNST) are important brain regions that regulate anxiety. This study aims to explore the effect of quercetin on anxiety-like behaviors, as well as the underlying mechanisms associated with neuroinflammation in the LH and BNST.</p><p><strong>Methods: </strong>The anxiety models were established in male mice by chronic restraint stress (CRS) and lipopolysaccharide (LPS) administration. The elevated plus maze (EPM) and open field (OF) tests were used to evaluate anxiety level. Immunofluorescent staining and quantitative real-time PCR were performed to examine the expression of microglia and inflammatory cytokines in the LH and BNST of male mice.</p><p><strong>Results: </strong>Behavioral data showed that quercetin treatment in male mice significantly alleviated anxiety in the EPM and OF tests. Examination of the inflammation level further revealed that quercetin administration significantly inhibited microglia activation in the LH and BNST of CRS- and LPS-treated male mice, while concurrently reducing the levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in the LH of CRS-treated male mice, as well as interleukin-1β (IL-1β) mRNA expression in the LH of LPS-treated male mice. Furthermore, we found that the expression of NF-κB was downregulated by quercetin in the LH of CRS-treated male mice.</p><p><strong>Conclusion: </strong>Our study indicates the clinical potential of quercetin in neuroinflammation-related anxiety, and begins to show that the underlying mechanism in the chronic restraint stress condition may potentially involve the modulation of NF‑κB signaling pathway in the LH.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2063-2076"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014156","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":"Disruptive effects of d-amphetamine on conditioned sexual inhibition in the male rat.","authors":"Katuschia Germé, Dhillon Persad, Justine Petit-Robinson, Shimon Amir, James G Pfaus","doi":"10.1007/s00213-025-06786-y","DOIUrl":"10.1007/s00213-025-06786-y","url":null,"abstract":"<p><strong>Rationale: </strong>Male rats trained to associate a neutral odor (almond) with nonreceptive females during their initial sexual experiences develop a conditioned sexual inhibition (CSI) toward the female bearing the olfactory cue when given a choice in a final copulatory preference test between two receptive females (one unscented and one scented) in an open field. We have previously shown that this CSI can be abolished by acute alcohol before the final copulatory preference test.</p><p><strong>Objective: </strong>To examine whether acute treatment with d-amphetamine could also disrupt CSI.</p><p><strong>Methods: </strong>Male rats received 20 alternating conditioning sessions with an unscented receptive female or an almond-scented non-receptive female. Forty minutes prior to the copulatory preference test with two receptive females, one unscented and the other scented (almond extract), males were injected with saline or one of three doses of d-amphetamine (d- 0.5, 1.0, or 2.0 mg/kg). After two reconditioning trials, males were injected with d-amp or saline and exposed to the olfactory cue alone for 1 h. Brains were fixed and processed for immunohistochemical analysis of Fos protein as a marker of neuronal activation. Fos expression was assessed in several brain regions involved in male sexual behavior.</p><p><strong>Results: </strong>Saline-treated males displayed inhibition of copulatory behavior directed toward the scented female. In contrast, and regardless of the dose, males treated with d-amp prior to the final test copulated with both scented and unscented females, indicating that d-amp disrupted the CSI. Exposure to d-amphetamine and the odor alone induced a differential pattern of Fos expression in several brain areas involved in the expression and/or the regulation of male sexual behavior.</p><p><strong>Conclusions: </strong>As observed previously with alcohol, a low dose of d-amphetamine disrupted the display of a CSI by acting on brain regions mediating sexual behavior.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2097-2110"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025537","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}