Pharmacology Biochemistry and Behavior最新文献

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ANXIOLYTICS: Origins, drug discovery, and mechanisms 解毒剂:起源、药物发现和机制。
IF 3.3 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2024-08-22 DOI: 10.1016/j.pbb.2024.173858
{"title":"ANXIOLYTICS: Origins, drug discovery, and mechanisms","authors":"","doi":"10.1016/j.pbb.2024.173858","DOIUrl":"10.1016/j.pbb.2024.173858","url":null,"abstract":"<div><p>Anxiety is a part of the human condition and has been managed by psychoactive substances for centuries. The current medical need and societal demand for anxiolytic medicines has not abated. The present overview provides a brief historical introduction to the discovery of modern age anxiolytics that include the benzodiazepines together with a discussion of the continuing medical need for new antianxiety medications. The paper also discusses the use and impact of behavioral pharmacology in the preclinical development of anxiolytics. The review then highlights the diversity of mechanisms for creating a new generation of anxiolytics through mechanisms beyond the potentiation of GABA<sub>A</sub> receptors and the blockade of monoamine uptake. A discussion then follows on the behavioral specificity of action of anxiolytics that includes the concept of creating an anxioselective drug, one that targets anxiety without producing untoward effects that include sedation and dependence. The use of anxiolytics in the treatment of other conditions such as substance use disorder is also briefly reviewed. Finally, a brief summary of the current status of anxiolytic drug development is provided. The review concludes with the idea that despite a host of anxiolytic drugs, the lack of efficacy in some patients and the side-effects and safety issues associated with some of these medications demands alternative medicines. Current preclinical and clinical research is ongoing with the goal of identifying such compounds.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047030","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}
引用次数: 0
Gender differences in the relationship between nicotine exposure and symptoms of depression 尼古丁暴露与抑郁症状之间的性别差异。
IF 3.3 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2024-08-21 DOI: 10.1016/j.pbb.2024.173857
{"title":"Gender differences in the relationship between nicotine exposure and symptoms of depression","authors":"","doi":"10.1016/j.pbb.2024.173857","DOIUrl":"10.1016/j.pbb.2024.173857","url":null,"abstract":"<div><h3>Background</h3><p>Tobacco-derived nicotine exposure is linked to depression. However, the associations of nicotine and its metabolites with symptoms of depression, particularly concerning gender differences, remain underexplored.</p></div><div><h3>Methods</h3><p>The characteristics and total nicotine equivalents (TNE) of 1001 subjects were determined. The association between the TNE and symptoms of depression, accounting for gender differences, was investigated using generalized linear models and subgroup analyses.</p></div><div><h3>Results</h3><p>Men exhibited significantly greater levels of the nicotine exposure indicators TNE2, TNE3, TNE6, and TNE7 (<em>P</em> &lt; 0.005). A significantly greater percentage of women (23.45 %) than men (9.81 %) exhibited symptoms of depression (<em>P</em> &lt; 0.0001). In women, the relationship between the TNE and depression was reflected by a U-shaped curve with significant inflection points, particularly for TNE3, TNE6, and TNE7. Furthermore, in women, concentrations above 48.98 nmol/mL for TNE3, 53.70 nmol/mL for TNE6, and 57.54 nmol/mL for TNE7 were associated with 154 %, 145 %, and 138 % increases in the risk of depression, respectively. In contrast, these associations did not reach significance among men.</p></div><div><h3>Limitations</h3><p>The cross-sectional design limits the ability to infer causality between nicotine exposure and depressive symptoms. Larger-scale studies are needed to confirm these findings.</p></div><div><h3>Conclusions</h3><p>Gender could be a significant factor influencing the relationship between nicotine exposure levels and symptoms of depression. The impact of nicotine exposure on symptoms of depression should be particularly considered among women.</p></div><div><h3>Implications</h3><p>This study revealed the complex relationship between tobacco-related nicotine exposure and depressive symptoms, with a particular focus on gender differences. Our results revealed a distinct U-shaped correlation between total nicotine equivalents and depression in women, which differed from that in men. These findings emphasize the importance of tailoring clinical approaches to address nicotine exposure and manage depressive symptoms based on gender.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000517","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}
引用次数: 0
Lower distress intolerance is associated with higher glutathione levels in adolescent cannabis users 在青少年大麻使用者中,较低的痛苦不耐受性与较高的谷胱甘肽水平有关。
IF 3.3 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2024-08-20 DOI: 10.1016/j.pbb.2024.173861
{"title":"Lower distress intolerance is associated with higher glutathione levels in adolescent cannabis users","authors":"","doi":"10.1016/j.pbb.2024.173861","DOIUrl":"10.1016/j.pbb.2024.173861","url":null,"abstract":"<div><p>Cannabis (CB) use and psychological stressors increase oxidative stress in the brain. Glutathione (GSH), the most abundant antioxidant in the brain, protects against oxidative stress. Furthermore, distress intolerance, the inability to tolerate psychological or physiological stress is a risk factor for CB use. The relationship between CB use, brain GSH levels and distress intolerance remains unknown. Therefore, we examined GSH levels in the anterior cingulate cortex (ACC), as a measure of oxidative stress, and its relationship with distress intolerance in adolescent CB users and healthy controls (HC).</p><p>Sixteen HC and 17 CB-using adolescents were included in the analysis. GSH levels were measured in the ACC using a metabolite-edited proton magnetic resonance spectroscopy sequence on a 3T scanner. Distress intolerance was assessed using the Distress Intolerance Index (DII) and CB use was evaluated using a structured clinical interview.</p><p>In the CB group, lower CSF-corrected GSH levels in the ACC were correlated with higher DII scores. However, no significant between group differences were observed for ACC CSF-corrected GSH levels or on DII scores. No significant correlations were observed in the HC group between GSH levels and DII.</p><p>Our findings suggests that the association between lower GSH levels and greater distress intolerance in CB users might reflect alterations in the balance between protective and oxidative stress conditions linked to the ability to tolerate distress. Further examination into this relationship can provide important insights into neurobiological correlates and risk factors associated with CB use to help inform preventive and treatment targets in the future.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018230","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}
引用次数: 0
The effects of intra-accumbal administration of the nicotinic acetylcholine receptor agonist cytisine on the operant oral self-administration of ethanol were prevented by the GABAB receptor agonist baclofen in rats GABAB受体激动剂巴氯芬可阻止大鼠体内累积给药烟碱乙酰胆碱受体激动剂胞嘧啶对乙醇操作性口服自我给药的影响。
IF 3.3 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2024-08-17 DOI: 10.1016/j.pbb.2024.173850
{"title":"The effects of intra-accumbal administration of the nicotinic acetylcholine receptor agonist cytisine on the operant oral self-administration of ethanol were prevented by the GABAB receptor agonist baclofen in rats","authors":"","doi":"10.1016/j.pbb.2024.173850","DOIUrl":"10.1016/j.pbb.2024.173850","url":null,"abstract":"<div><h3>Rationale</h3><p>Although the mesocorticolimbic dopamine (DA) system is the main neurochemical substrate that regulates the addictive and reinforcing effects of ethanol (EtOH), other neurotransmitter systems, such as the acetylcholine (Ach) system, modulate DAergic function in the nucleus accumbens (nAcc). Previously, we reported that intra-nAcc administration of the nicotinic Ach receptor agonist cytisine increased oral EtOH self-administration. GABAB receptors in the nAcc are expressed in DAergic terminals, inhibit the regulation of DA release into the nAcc, and could modulate the effects of cytisine on oral EtOH self-administration. The present study assessed the effects of intra-nAcc administration of the GABAB receptor agonist baclofen (BCF) on the impacts of cytisine on oral EtOH self-administration. Methods: Male Wistar rats were deprived of water for 23.30 h and then trained to press a lever to receive EtOH on an FR3 schedule until a stable response rate of 80 % was achieved. After this training, the rats received an intra-nAcc injection of the nAch receptor agonist cytisine, BCF, and cytisine or 2-hydroxysaclofen, BCF, and cytisine before they were given access to EtOH on an FR3 schedule. Results: Intra-nAcc injections of cytisine increased oral EtOH self-administration; this effect was reduced by BCF, and 2-hydroxysaclofen blocked the effects of BCF. Conclusions: These findings suggest that the reinforcing effects of EtOH are modulated not only by the DA system but also by other neurotransmitter systems involved in regulating DA release from DAergic terminals.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004977","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}
引用次数: 0
Kappa opioid receptor mediated operant performance in male and female rats 雌雄大鼠的 Kappa 阿片受体介导的操作表现。
IF 3.3 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2024-08-14 DOI: 10.1016/j.pbb.2024.173847
{"title":"Kappa opioid receptor mediated operant performance in male and female rats","authors":"","doi":"10.1016/j.pbb.2024.173847","DOIUrl":"10.1016/j.pbb.2024.173847","url":null,"abstract":"<div><p>Anhedonia and avolition are emotions frequently endorsed by individuals with stress related disorders. Kappa opioid receptor (KOR) activation can induce negative emotions and recent clinical evidence suggests that KOR antagonism can alleviate anhedonia in a transdiagnostic cohort of patients. However, the behavioral consequences of KOR activation and antagonism in modulating motivation, as assessed by schedule-controlled behavioral performance without preexisting conditions (stress or substance use), have not been formally assessed. To address this gap in the literature, this report utilized male and female Sprague Dawley rats to (1) evaluate the impact of the selective KOR agonist U50,488, on the performance of animals responding for sucrose pellets under a progressive ratio (PR) schedule and (2) determine the effects of the short-acting KOR antagonist LY2444296 alone and on U50,488 mediated reductions in PR performance. Overall, U50,488 5 mg/kg significantly reduced the breakpoint and number of rewards obtained by animals. This occurred in the absence of motor impairment and independent of evidence for satiation. LY2444296 did not alter PR performance when administered alone but effectively blocked the deficits induced by U50,488. To further delineate the behavioral alterations that underlie these reductions in responding, a more detailed analysis was conducted on PR performance in the first 15 min of the session, the period of time when animals obtained the most reinforcers. During this period, U50,488 increased the length of the post-reinforcement pause and reduced the running rate on PR schedules. These changes in behavior produced by acute activation of KORs are consistent with a reduction of effort-related motivation in rodents. These data contribute to the understanding of how KORs modulate motivation, which is critical to future efforts to evaluate performance in the context of stress and assess how KOR antagonists alleviate anhedonic behaviors associated with stress.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996255","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}
引用次数: 0
Maternal fluoxetine impairs synaptic transmission and plasticity in the medial prefrontal cortex and alters the structure and function of dorsal raphe nucleus neurons in offspring mice 母体氟西汀会损害后代小鼠内侧前额叶皮层的突触传递和可塑性,并改变背侧剑突核神经元的结构和功能。
IF 3.3 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2024-08-13 DOI: 10.1016/j.pbb.2024.173849
{"title":"Maternal fluoxetine impairs synaptic transmission and plasticity in the medial prefrontal cortex and alters the structure and function of dorsal raphe nucleus neurons in offspring mice","authors":"","doi":"10.1016/j.pbb.2024.173849","DOIUrl":"10.1016/j.pbb.2024.173849","url":null,"abstract":"<div><p>Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are commonly prescribed to women during pregnancy and breastfeeding despite posing a risk of adverse cognitive outcomes and affective disorders for the child. The consequences of SSRI-induced excess of 5-HT during development for the brain neuromodulatory 5-HT system remain largely unexplored. In this study, an SSRI - fluoxetine (FLX) - was administered to C57BL/6 J mouse dams during pregnancy and lactation to assess its effects on the offspring. We found that maternal FLX decreased field potentials, impaired long-term potentiation, facilitated long-term depression and tended to increase the density of 5-HTergic fibers in the medial prefrontal cortex (mPFC) of female but not male adolescent offspring. These effects were accompanied by deteriorated performance in the temporal order memory task and reduced sucrose preference with no change in marble burying behavior in FLX-exposed female offspring. We also found that maternal FLX reduced the axodendritic tree complexity of 5-HT dorsal raphe nucleus (DRN) neurons in female but not male offspring, with no changes in the excitability of DRN neurons of either sex. While no effects of maternal FLX on inhibitory postsynaptic currents (sIPSCs) in DRN neurons were found, we observed a significant influence of FLX exposure on kinetics of spontaneous excitatory postsynaptic currents (sEPSCs) in DRN neurons. Finally, we report that no changes in field potentials and synaptic plasticity were evident in the mPFC of the offspring after maternal exposure during pregnancy and lactation to a new antidepressant, vortioxetine. These findings show that in contrast to the mPFC, long-term consequences of maternal FLX exposure on the structure and function of DRN 5-HT neurons are mild and suggest a sex-dependent, distinct sensitivity of cortical and brainstem neurons to FLX exposure in early life. Vortioxetine appears to exert fewer side effects with regards to the mPFC when compared with FLX.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0091305724001436/pdfft?md5=3947b1857945be9a5cf2da067cf54531&pid=1-s2.0-S0091305724001436-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drug discrimination learning: Interoceptive stimulus control of behavior and its implications for regulated and dysregulated drug intake 药物辨别学习:感知间刺激对行为的控制及其对调节和失调药物摄入的影响。
IF 3.3 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2024-08-11 DOI: 10.1016/j.pbb.2024.173848
{"title":"Drug discrimination learning: Interoceptive stimulus control of behavior and its implications for regulated and dysregulated drug intake","authors":"","doi":"10.1016/j.pbb.2024.173848","DOIUrl":"10.1016/j.pbb.2024.173848","url":null,"abstract":"<div><p>Drug discrimination research has generated rich evidence for the capacity of interoceptive drug stimuli to control behavior by serving as discriminative cues. Owing to its neuropharmacological specificity, drug discrimination learning has been widely used to characterize the stimulus effects and neuropharmacological underpinning of drugs. Apart from such utility, discriminative drug stimuli may help regulate drug use by disambiguating conditioned associations and post-intake outcomes. First, this review summarizes the evidence supporting interoceptive regulation of drug intake from the literature of exteroceptive discriminative control of drug-related behavior, effects of drug priming, and self-titration of drug intake. Second, an overview of interoceptive control of reward-seeking and the animal model of discriminated goal-tracking is provided to illustrate interoceptive stimulus control of the initiation and patterning of drug intake. Third, we highlight the importance of interoceptive control of aversion-avoidance in the termination of drug-use episodes and describe the animal model of discriminated taste avoidance that supports such a position. In bridging these discriminative functions of drug stimuli, we propose that interoceptive drug stimuli help regulate intake by disambiguating whether intake will be rewarding, nonrewarding, or aversive. The reflection and discussion on current theoretical formulations of interoceptive control of drug intake may further scientific advances to improve animal models to study the mechanisms by which interoceptive stimuli regulate drug intake, as well as how alterations of interoceptive processes may contribute to the transition to dysregulated drug use.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976325","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}
引用次数: 0
Anxiolytic treatment of a trapped rat reduces helping and anxiogenic treatment increases helping: Evidence for emotional contagion in altruism 对被困大鼠进行抗焦虑治疗会减少助人行为,而抗焦虑治疗则会增加助人行为:利他主义情绪传染的证据。
IF 3.3 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2024-08-08 DOI: 10.1016/j.pbb.2024.173846
{"title":"Anxiolytic treatment of a trapped rat reduces helping and anxiogenic treatment increases helping: Evidence for emotional contagion in altruism","authors":"","doi":"10.1016/j.pbb.2024.173846","DOIUrl":"10.1016/j.pbb.2024.173846","url":null,"abstract":"<div><p>The present experiment used the trapped rat model to explore whether pharmacological manipulation of distress affects the likelihood of helping behavior. 120 Sprague-Dawley rats (30 male pairs and 30 female pairs) completed 12 consecutive, daily trials assessing helping behavior. During an individual trial, a trapped rat was placed in a restrainer in the center of an open field, while its cagemate could move around freely and possibly open the restrainer by lifting a door. Trapped rats received an intraperitoneal injection of either 1) physiological saline, 2) the anxiolytic midazolam (1.5 mg/kg), or 3) the anxiogenic yohimbine (2.5 mg/kg) 30 min prior to the start of each trial. Dependent variables measured were: 1) door opening latency (<em>sec</em>), 2) percentage of trials in which a door opening occurred, and 3) the number of free rats classified as “openers.” Based on emotional contagion theory, we predicted that 1) free rats paired with midazolam-subjects would show attenuated helping behavior (e.g., higher door opening latency) compared to controls, and conversely 2) free rats paired with yohimbine-subjects would show enhanced helping behavior. First, a significant sex-difference was observed, in that more females were classified as openers than males. This supports previous evidence that females express higher altruistic motivation and experience stronger emotional contagion than males. Second, midazolam-treatment significantly attenuated helping behavior. From trials 4–12, free rats paired with midazolam-subjects expressed slower door opening latencies compared to controls. Third, yohimbine-treatment significantly increased helping behavior (e.g., reduced door opening latencies) – but only on trials 1–3; by trials 9–12, this pattern was reversed. These results are consistent with emotional contagion theory and indicate that intensity of distress directly modulates altruistic motivation through vicarious state-matching.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913661","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}
引用次数: 0
Kappa-opioid receptor antagonism in the nucleus accumbens shell distinguishes escalated alcohol consumption and negative affective-like behavior from physiological withdrawal in alcohol-dependence 核团外壳中的卡巴-阿片受体拮抗作用可将酒精依赖症患者的酒精消费升级和负性情感样行为与生理戒断区分开来。
IF 3.3 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2024-08-07 DOI: 10.1016/j.pbb.2024.173840
{"title":"Kappa-opioid receptor antagonism in the nucleus accumbens shell distinguishes escalated alcohol consumption and negative affective-like behavior from physiological withdrawal in alcohol-dependence","authors":"","doi":"10.1016/j.pbb.2024.173840","DOIUrl":"10.1016/j.pbb.2024.173840","url":null,"abstract":"<div><p>Alcohol use disorder (AUD) is a chronic relapsing disease that is deleterious at individual, familial, and societal levels. Although AUD is one of the highest preventable causes of death in the USA, therapies for the treatment of AUD are not sufficient given the heterogeneity of the disorder and the limited number of approved medications. To provide better pharmacological strategies, it is important to understand the neurological underpinnings of AUD. Evidence implicates the endogenous dynorphin (DYN)/κ-opioid receptor (KOR) system recruitment in dysphoric and negative emotional states in AUD to promote maladaptive behavioral regulation. The nucleus accumbens shell (AcbSh), mediating motivational and emotional processes that is a component of the mesolimbic dopamine system and the extended amygdala, is an important site related to alcohol's reinforcing actions (both positive and negative) and neuroadaptations in the AcbSh DYN/KOR system have been documented to induce maladaptive symptoms in AUD. We have previously shown that in other nodes of the extended amygdala, site-specific KOR antagonism can distinguish different symptoms of alcohol dependence and withdrawal. In the current study, we examined the role of the KOR signaling in the AcbSh of male Wistar rats in operant alcohol self-administration, measures of negative affective-like behavior, and physiological symptoms during acute alcohol withdrawal in alcohol-dependence. To induce alcohol dependence, rats were exposed to chronic intermittent ethanol vapor for 14 h/day for three months, during which stable escalation of alcohol self-administration was achieved and pharmacological AcbSh KOR antagonism ensued. The results showed that AcbSh KOR antagonism significantly reduced escalated alcohol intake and negative affective-like states but did not alter somatic symptoms of withdrawal. Understanding the relative contribution of these different drivers is important to understand and inform therapeutic efficacy approaches in alcohol dependence and further emphasis the importance of the KOR/DYN system as a target for AUD therapeutics.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889902","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}
引用次数: 0
Age- and sex-driven alterations in alcohol consumption patterns: Role of brain ethanol metabolism and the opioidergic system in the nucleus accumbens 年龄和性别驱动的酒精消费模式改变:大脑乙醇代谢和伏隔核阿片能系统的作用
IF 3.3 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2024-08-03 DOI: 10.1016/j.pbb.2024.173845
{"title":"Age- and sex-driven alterations in alcohol consumption patterns: Role of brain ethanol metabolism and the opioidergic system in the nucleus accumbens","authors":"","doi":"10.1016/j.pbb.2024.173845","DOIUrl":"10.1016/j.pbb.2024.173845","url":null,"abstract":"<div><p>Alcohol consumption leads to significant neurochemical and neurobiological changes, contributing to the development of alcohol use disorders (AUDs), which exhibit sex- and age-dependent variations according to clinical data. However, preclinical studies often neglect these factors when investigating alcohol consumption patterns. In this study, we present data on male and female rats continuously exposed to a 20 % ethanol solution for one month. The animals were divided into two groups based on their age at the onset of drinking (8 and 12 weeks old). Interestingly, 12-week-old males consumed significantly less alcohol than both 12-week-old females and 8-week-old animals, indicating that alcohol consumption patterns vary with sex and age in our model. Additionally, to advance in the study of the neurobiological alterations induced by ethanol intake in the mesocorticolimbic system (MCLS) that may participate in its reinforcing properties and the maintenance of alcohol drinking behavior, we measured catalase activity—an enzyme involved in alcohol metabolism and related to ethanol reinforcement—in the nucleus accumbens (NAc) of these animals. Furthermore, we measured the levels of mu (MOR), kappa (KOR), delta (DOR), and nociceptin (NOP) opioid receptors in the NAc, as the endogenous opioidergic system plays a pivotal role in regulating the MCLS and alcohol reinforcement. MOR levels were lower in high alcohol-consuming groups (8-week-old males and all females). Both DOR and NOP levels decreased with age, whereas KOR levels remained unchanged. Our findings suggest that the age at onset of alcohol consumption critically influences alcohol intake, particularly in males. Additionally, females consistently showed higher alcohol intake regardless of age, highlighting inherent sex-specific differences. The dynamic changes in catalase activity and opioid receptor expression suggest the involvement of these factors in modulating alcohol consumption.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0091305724001394/pdfft?md5=eafd9709425dba6cfbb4b770ee7ade21&pid=1-s2.0-S0091305724001394-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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