Pharmacology Biochemistry and Behavior最新文献

{"title":"Different protocols of REM sleep deprivation led to controversial effects on OCD- and anxiety-like behaviors and locomotor activity in fear conditioning male and female rats with respect to BDNF expression level","authors":"Masoumeh Payamani ,&nbsp;Seyedeh-Tabassom Abdollahi-Keyvani ,&nbsp;Mandana Sajjadi ,&nbsp;Shahin Akhondzadeh ,&nbsp;Reihane Javid ,&nbsp;Reihaneh Nakhaei-Zadeh ,&nbsp;Marzieh Jalalian-Javadpour ,&nbsp;Salar Vaseghi","doi":"10.1016/j.pbb.2025.174027","DOIUrl":"10.1016/j.pbb.2025.174027","url":null,"abstract":"<div><div>Specific protocols of rapid-eye movement (REM) sleep deprivation (SD) may lead to behavioral phenotypes considered as obsessive-compulsive disorder (OCD)-like behavior and hyperactivity (mania-like behavior). The present study aimed to assess the effects of REM SD on both sexes of control and fear conditioning (FC) rats. REM SD was induced for 1 or 2 or 3 weeks (6 h/d). Freezing, locomotor activity, anxiety-like behavior, grooming and burying marbles (OCD-like behaviors), and brain-derived neurotrophic factor (BDNF) in the hippocampus were evaluated. The results showed 1w REM SD decreased freezing in females, while 2w and 3w REM SD decreased freezing in both sexes. Locomotor activity in 2w REM SD males was increased, while was decreased in 3w group. In females, both 2w and 3w REM SD increased locomotion. REM SD in both sexes increased locomotion in FC rats. All REM SD protocols decreased anxiety in both sexes of FC rats. REM SD in control and FC rats led to OCD-like behaviors. All REM SD protocols decreased BDNF in both sexes, while 3w slightly increased it, suggesting a compensatory mechanism over time. 2w and 3w REM SD increased BDNF in FC rats in both sexes. Pearson correlation test also showed that changes in BDNF levels may be related to some behavioral changes only in females. In conclusion, for the first time, the present study showed sex differences in the effects of REM SD on behavioral functions in control and FC rats, and in the relationship between BDNF levels and behavioral changes.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174027"},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898716","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":"Schizophrenia-like phenotypes and long-term synaptic plasticity impairment in GluN2A-transgenic mice","authors":"Huan Zhang ,&nbsp;Wen Si ,&nbsp;Bo Wang ,&nbsp;Jiao Han ,&nbsp;Fan Ding ,&nbsp;Qingsheng Xue ,&nbsp;Xiaohua Cao","doi":"10.1016/j.pbb.2025.174026","DOIUrl":"10.1016/j.pbb.2025.174026","url":null,"abstract":"<div><div>While <em>N</em>-methyl-<span>d</span>-aspartate receptor (NMDAR) hypofunction has been suggested as a hallmark of schizophrenia, the role of subunit-specific dysregulation such as GluN2A overexpression remains poorly understood. The present study comprehensively investigated the impact of GluN2A overexpression on behavioral phenotypes, cognitive functions, and synaptic plasticity in transgenic mice with forebrain-specific overexpression of the GluN2A subunit (GluN2A-TG). Behavioral assessments revealed schizophrenia-like phenotypes, including prolonged stereotypic movement duration, impaired sensorimotor gating, reduced social interaction, and diminished nest-building activity in GluN2A-TG mice. Consistently, GluN2A-TG mice exhibited not only deficits in spatial working memory and olfactory working memory but also impaired associative learning. In addition, both long-term potentiation and long-term depression were significantly attenuated in the prefrontal cortex (PFC) of GluN2A-TG mice. Furthermore, electrophysiological analysis of NMDAR-mediated excitatory postsynaptic currents in PFC neurons revealed altered kinetics characterized by a faster decay time and significantly increased amplitude in GluN2A-TG mice. Collectively, these findings suggest that GluN2A overexpression may induce schizophrenia-like phenotypes via impairing NMDAR-dependent long-term synaptic plasticity in the PFC, likely due to altered NMDAR subunit composition leading to disrupted calcium signaling dynamics. These results provide critical insights into the pathological role of GluN2A in schizophrenia.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174026"},"PeriodicalIF":3.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886798","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 ventral hippocampus mediates experience-dependent social modulation of fear in rats","authors":"Dan Tao ,&nbsp;Cuijie Shi ,&nbsp;Zhihao Song ,&nbsp;Jing Wen ,&nbsp;Yujun Gao ,&nbsp;Yixiao Luo ,&nbsp;Haishui Shi ,&nbsp;Shihao Huang","doi":"10.1016/j.pbb.2025.174016","DOIUrl":"10.1016/j.pbb.2025.174016","url":null,"abstract":"<div><div>Fear Conditioning by Proxy (FCbP) is a form of socially mediated fear learning, in which no-conditioned rodents acquire fear memories through social interactions with fear-conditioned rodents. This study investigates the impact of prior similar experiences on the transmission of contextual fear memories in FCbP and explores the role of the ventral hippocampus (vHPC) in the social transmission of fear. Observers were divided into two groups: those with contextual experience (D/O) and those without contextual experience- naïve (O). These rats were exposed to fear-conditioned demonstrators (D) through social interaction, and their responses to fear contexts were observed. Additionally, the effect of vHPC inactivation on fear memory transmission was examined by injecting lidocaine into the vHPC. Fear was transmitted through social interaction among experienced rats but not among naive rats. Furthermore, lidocaine injection into the vHPC inhibited the social transmission of fear memories among experienced rats. This study demonstrates that contextual fear memories can be transmitted through social interaction among experience-dependent rats but not among naive rats. That inactivation in the vHPC blocks the social transmission of contextual fear memories.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174016"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877165","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":"Drosophila model of depression-like behavior: systematic investigation of external stress parameters and intrinsic susceptibility","authors":"Wenhao Zhang ,&nbsp;Zhifu Ai ,&nbsp;Genhua Zhu ,&nbsp;Ming Yang ,&nbsp;Yali Liu ,&nbsp;Huanhua Xu ,&nbsp;Qin Zheng ,&nbsp;Yonggui Song ,&nbsp;Dan Su","doi":"10.1016/j.pbb.2025.174014","DOIUrl":"10.1016/j.pbb.2025.174014","url":null,"abstract":"<div><div>Currently, <em>Drosophila</em> is widely used to study brain diseases. Unfortunately, <em>Drosophila</em> still lacks a mature and stable model for research on depression. This study addressed this issue by systematically exploring external stress and intrinsic susceptibility factors (<em>Drosophila</em> strains, adult/larval forms) that may influence the establishment and reproducibility of the stress-induced model. On this basis, the parameters are optimized. The results indicate <em>Drosophila</em> strains and forms are critical factors influencing model establishment, while external stress is the primary cause affecting the model's mortality rate. Compared with the other four strains, Canton-S are the most susceptible to chronic unpredictable mild stress (CUMS). Larval forms exhibit lower reactivity to external stress compared to adults. Parameter variations greatly influence model mortality rates from cold/heat/starvation stress. The model methodology validation study conducted subsequently through assessments of face, construct, and predictive validity demonstrates that the model exhibits face (neurobehavioral differences), structural (neurotransmitter changes in the <em>Drosophila</em> brain), and predictive (behavioral changes after fluoxetine treatment) validity. Additionally, spatial behavior experiments in <em>Drosophila</em> provide more realistic activity patterns compared to planar behavior, minimizing potential errors in interpreting lateral movements of the <em>Drosophila</em>, and it is recommended that this metric be included in model evaluation. This study presents a comprehensive set of methods for establishing and evaluating a depression-like behavior model and offers greater convenience for research on the pathogenesis of depression, as well as the screening, efficacy evaluation, and mechanistic studies of antidepressant drugs.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174014"},"PeriodicalIF":3.3,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859028","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 dosage-dependent effects of cevimeline in preventing clozapine-induced dyslipidaemia in female rats","authors":"Jiamei Lian ,&nbsp;Bo Pan ,&nbsp;Chao Deng","doi":"10.1016/j.pbb.2025.174017","DOIUrl":"10.1016/j.pbb.2025.174017","url":null,"abstract":"<div><div>Clozapine is the most effective second-generation antipsychotic drug, especially for the therapy of treatment-resistant schizophrenia. However, it is associated with metabolic side-effects. Clozapine has a high antagonistic affinity to muscarinic M3 receptors, which has been reported to play a significant role in these side-effects. This study aimed to investigate whether co-administration of cevimeline (an M3 receptor agonist) could prevent the metabolic disorders induced by clozapine. Female Sprague Dawley rats were treated orally with clozapine (20 mg/kg, 3 times daily) and/or cevimeline at three dosages (3, 6, 9 mg/kg, 3 times daily), or a vehicle for two weeks. Body weight gain, food/water intake, and temperature were recorded. Open field tests were performed to assess motor activity. Clozapine only treatment significantly decreased body weight gain, feeding efficiency, perirenal, periovary, inguinal, total white fat mass, and NEFA levels. The reduction in body weight gain and feeding efficiency caused by clozapine was partially reversed by co-treatment with 3 or 6 mg/kg cevimeline. Clozapine also significantly increased the liver mass, LDL, and HDL level, which were reversed by the co-treatment with cevimeline at all tested dosages. These results support further clinical trials to evaluate cevimeline's potential in controlling clozapine-induced dyslipidemia.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174017"},"PeriodicalIF":3.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863517","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":"Pre-exposure to eutylone attenuates its own aversive effects but has no impact on cocaine or MDMA: A possible role of eutylone's hybrid pharmacology","authors":"Negar G. Ardabili,&nbsp;Shira Tan,&nbsp;Anthony L. Riley","doi":"10.1016/j.pbb.2025.174013","DOIUrl":"10.1016/j.pbb.2025.174013","url":null,"abstract":"<div><div>Previous research has reported that pre-exposure to a variety of drugs of abuse can impact (reduce) the aversive effects of themselves and other abused compounds, often as a function of their shared pharmacological activity. In this context, the present series of studies investigated the effects of history with the synthetic cathinone eutylone on the aversive effects of cocaine, MDMA, and itself in adult, male Sprague-Dawley rats. Given eutylone's structural similarities with its parent compound methylone, it was predicted that its ability to attenuate cocaine- and MDMA-induced taste avoidance would parallel the effects of methylone pre-exposure in this design (cocaine &gt; MDMA). In Experiment 1, male Sprague-Dawley rats were exposed to eutylone (20 mg/kg, IP) or equivolume saline every other day for five exposures followed by taste avoidance conditioning with 20 mg/kg cocaine (SC) or 1.8 mg/kg MDMA (SC). Both cocaine and MDMA induced significant taste avoidance that developed over repeated conditioning trials. Cocaine and MDMA-induced avoidance were unaffected by eutylone history. To assess the general ability of eutylone pre-exposure to attenuate taste avoidance conditioning in the pre-exposure design, in Experiment 2, an additional set of male Sprague-Dawley rats was injected with 20 mg/kg eutylone (IP) prior to taste avoidance conditioning with eutylone (20 mg/kg (IP). Under these conditions, eutylone-induced avoidance was attenuated by eutylone pre-exposure. Given that eutylone history attenuated eutylone-induced avoidance argues that the failure to affect cocaine or MDMA was not a function of eutylone in this preparation. The inability of eutylone to attenuate the aversive effects of cocaine and MDMA despite sharing pharmacological activity suggests that eutylone's hybrid pharmacology may create a unique interoceptive effect different than that produced by either drug.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174013"},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859029","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":"Psychostimulant induced behavioral sensitization: The contribution of drug stimuli to context and Pavlovian conditioned stimuli","authors":"Robert J. Carey","doi":"10.1016/j.pbb.2025.174011","DOIUrl":"10.1016/j.pbb.2025.174011","url":null,"abstract":"<div><div>The drug induced enhancement of behavioral stimulation effects with repeated drug treatments is frequently context specific implicating associative processes. Attempts to label these effects as Pavlovian conditioned drug responses have generally been dismissed as it has frequently been demonstrated that the test environment cues alone are insufficient to elicit the sensitized drug response. In this paper evidence will be presented showing that the sensitized drug response can in fact be elicited by test environment cues in a non-drug test. The key reason test environment cues alone are an inadequate conditioned stimulus to elicit the sensitized drug response with commonly used behavioral sensitization protocols is because drug stimulus cues of the drug used to induce behavioral sensitization are conflated with the test environment cues so that the conditioned stimulus has been transformed into a compound conditioned stimulus comprised of the test environment cues co-mingled with the drug stimulus cues In this paper we will present evidence that shows that modifications in the drug testing protocol such as placement of the subject into the test environment immediately after drug administration so that the test environment cues precede the onset of the drug response creates the opportunity for a Pavlovian test environment/drug response association. Also, the use of posttest drug administration can enable the test environment stimulus trace to be selectively paired with the drug response and acquire conditioned stimulus properties and become sufficient to elicit the sensitized behavioral drug response. From a Pavlovian conditioning perspective, repeated pairing of the drug with the test environment enables the conditioned drug response test response to add to the unconditioned drug response to generate a behavioral sensitization effect. Critically, the context needs to be recognized as a conditioned stimulus composite comprised of the test environment cues coupled with the drug generated stimulus cues.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"251 ","pages":"Article 174011"},"PeriodicalIF":3.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796115","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":"Systematic review and meta-analysis of weight gain and metabolic changes in children and adolescents using second-generation antipsychotics","authors":"Suzana Figueiredo Collares ,&nbsp;Antônio Márcio de Ávila Júnior ,&nbsp;Tamires Coelho Martins ,&nbsp;Victhor Hugo Martins Rezende ,&nbsp;Marco Aurélio Romano-Silva ,&nbsp;Renata Maria Silva Santos ,&nbsp;Débora Marques de Miranda","doi":"10.1016/j.pbb.2025.174012","DOIUrl":"10.1016/j.pbb.2025.174012","url":null,"abstract":"<div><div>The use of second-generation antipsychotics in children and adolescents has significantly increased in recent decades, raising concerns about side effects such as weight gain, dyslipidemia, and insulin resistance. These effects are concerning during development, as they may predispose individuals to adult obesity and metabolic complications. Therefore, the aim of this review is to update the evidence on associations between the use of these medications, weight gain, BMI changes, and major metabolic alterations in children and adolescents. This review was conducted following the PRISMA protocol and registered in PROSPERO under the number: CRD42024549448. The search was carried out in March 2024 using the terms “child,” “adolescent,” “weight gain,” “metabolism disorders,” and “antipsychotics,” combined with the AND operator in the MEDLINE, Scopus, Cochrane, and PubMed databases. The main findings of this review included weight gain, increased BMI, and metabolic alterations, such as insulin resistance and increased abdominal circumference. The meta-analysis highlighted a positive association between one of the investigated second-generation antipsychotics and weight gain. Therefore, prescriptions may be accompanied by strict guidelines for nutritional monitoring and metabolic control interventions.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"251 ","pages":"Article 174012"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780840","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":"Monoamine receptors targeted by methamphetamine differentially modulate basal and fentanyl-depressed respiration in mice","authors":"Harrison J. Elder ,&nbsp;D. Matthew Walentiny ,&nbsp;Patrick M. Beardsley","doi":"10.1016/j.pbb.2025.174004","DOIUrl":"10.1016/j.pbb.2025.174004","url":null,"abstract":"<div><h3>Rationale</h3><div>Fentanyl remains the primary cause of fatal overdoses, and its co-use with methamphetamine is a growing concern. Our lab previously demonstrated that racemic methamphetamine could have either respiratory stimulant or depressant effects depending on dose and separately determined by its enantiomers, dextromethamphetamine, and levomethamphetamine, respectively. Enantiomeric separation of methamphetamine's stimulant and depressant effects indicates that differences in their pharmacology might be exploited to develop novel respiratory stimulants. It is presently unknown which of methamphetamine's monoamine receptor mechanisms mediate these respiratory effects. Thus, systematic evaluation of monoamine receptor-selective agents may identify treatment targets for OIRD.</div></div><div><h3>Methods</h3><div>Six selective agonists at monoamine receptors involved in methamphetamine's activity [phenylephrine (PNE; α₁), clonidine (CLON; α₂), SKF-82958 (SKF; D₁), quinpirole (QPR; D₂-like), 8-OH-DPAT (8-OH; 5HT_1A), and DOI (5HT₂)] were tested in adult male mice to determine their effects on basal and fentanyl-depressed minute volume (MVb; i.e., respiratory frequency x tidal volume) using whole-body plethysmography. Agonists were initially tested at three behaviorally active doses for their effects on basal MVb. Agonists that stimulated respiration or did not decrease respiration were then tested in combination with fentanyl.</div></div><div><h3>Results</h3><div>The α₁ and D₁ agonists PNE and SKF dose-dependently increased basal MVb while the α₂ and D₂-like agonists CLON and QPR depressed basal MVb. Neither serotonin receptor agonist significantly altered basal MVb. Under fentanyl-depressed conditions, SKF produced transient but significant increases in MVb, while PNE more persistently elevated it. Interestingly, DOI transiently elevated depressed MVb, while 8-OH further exacerbated OIRD.</div></div><div><h3>Conclusions</h3><div>Selective activation of monoamine receptors alters basal respiration and OIRD, with D₁ and α₁ receptors representing potential targets as respiratory stimulants, whereas α₂, D₂-like, and 5HT_1A receptors may mediate the exacerbation of OIRD by methamphetamine.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"251 ","pages":"Article 174004"},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739799","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":"Agomelatine with cognitive behavioral therapy reduces insomnia severity index and subjective units of distress scores than initial-dose clonazepam in moderate to severe insomnia patients: A quasi-experimental study","authors":"Kousalya Prabahar ,&nbsp;Abinaya Ravikumar ,&nbsp;Anu Priya Jeyabalan ,&nbsp;Bharath Ravi ,&nbsp;Chandini Ravikumar ,&nbsp;Nithishadevi PannirukaiSelvan ,&nbsp;Saleh F. Alqifari ,&nbsp;Varadharajan Sivaraman ,&nbsp;Natarajan Shanmugasundaram ,&nbsp;Karthik Sankar","doi":"10.1016/j.pbb.2025.174003","DOIUrl":"10.1016/j.pbb.2025.174003","url":null,"abstract":"<div><h3>Background</h3><div>Insomnia can be caused by various factors including lack of sleep, stress, sadness, hormonal changes, excessive caffeine, anxiety, mental health disorders, and medications. Treatments include finding the cause, improving sleep patterns, using behavioral therapy, and taking sleeping pills in most cases. However, the drugs often cause worse side effects than insomnia. This study compared the efficacy of initial agomelatine and clonazepam doses with cognitive behavioral therapy for insomnia (CBT-i) in moderate to severe insomnia patients.</div></div><div><h3>Methods</h3><div>This quasi-experiment study involved 230 moderate to severe insomnia patients with group A as clonazepam 0.25 mg and B as agomelatine 25 mg. CBT-i was received by both of the groups and the Insomnia Severity Index (ISI), Subjective Units of Distress Scale (SUDS) score, medication adherence, and Adverse Drug Reactions (ADRs) were followed for up to 24 weeks.</div></div><div><h3>Results</h3><div>In the comparative analysis between and within groups, group B exhibited a significant reduction in ISI (<em>p</em> = 0.001) and SUDS (p = 0.001) scores at week 24 compared to group A. Overall, both groups demonstrated improved adherence. However, 12 patients in group A and 10 in group B experienced ADR, which included drowsiness, hypersalivation, diarrhea, maculopapular rash, and myotoxicity. The clonazepam-treated group showed reduced efficacy from week 12 onwards in the ISI and from week 16 in the SUDS median score, which was not observed in the agomelatine group.</div></div><div><h3>Conclusion</h3><div>The initial dose of agomelatine with CBT-i has a better impact on improving moderate to severe insomnia than the initial dose of clonazepam with CBT-i.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"251 ","pages":"Article 174003"},"PeriodicalIF":3.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743557","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}