多次鞘内注射不同剂量左旋精氨酸对福尔马林诱导的大鼠行为痛反应的影响(英文)

目的探讨不同剂量的一氧化氮(NO)对炎性痛的作用及其机制。方法大鼠鞘内每天注入一氧化氮的前体左旋精氨酸(L-Arg)10μg(低剂量组),250μg(高剂量组)或生理盐水(对照组),共持续4天。随后在大鼠右后爪掌皮下注射2%甲醛溶液(100μL),并在之后的1h内观察大鼠舔咬后爪的痛行为反应,4h后用免疫细胞化学技术检测大鼠脊髓背角c-Fos蛋白和神经元型一氧化氮合酶(nNOS)的表达。结果福尔马林引起的大鼠舔咬后爪的痛行为反应有两个时相。第一相的急性痛行为反应在各组间无明显差异。对于第二相的慢性痛行为反应累计时间以及脊髓背角c-Fos和nNOS的表达水平,低剂量组较对照组显著降低,而高剂量组较对照组显著升高。结论不同剂量的一氧化氮对脊髓痛觉的调制作用具有双面性,小剂量具有镇痛作用而大剂量具有促痛作用。     

NMDA受体激活诱导甲醛炎性痛大鼠脊髓HO-1蛋白表达增加

目的本实验通过在甲醛炎性痛大鼠鞘内注射N-甲基-D-d门冬氨酸(NMDA)受体抑制剂地卓西平马来酸盐(MK-801)以及在正常大鼠鞘内注射NMDA受体激动剂NMDA,观察二者对甲醛炎性痛大鼠以及正常大鼠脊髓血红素氧合酶-1(HO-1)表达的影响,探讨甲醛炎性痛诱导的大鼠脊髓HO-1蛋白表达改变是否受NMDA受体激活的影响。方法采用右后掌足底注射甲醛复制炎性痛模型,采用免疫组织化学方法观察脊髓HO-1蛋白表达。结果甲醛炎性痛大鼠L5脊髓后角Ⅰ-Ⅱ板层HO-1蛋白免疫反应阳性细胞数目、平均光密度值均明显大于正常对照组,预先鞘内注射MK-801可明显抑制甲醛炎性痛诱导的大鼠双侧脊髓后角Ⅰ-Ⅱ板层HO-1蛋白的表达,正常大鼠鞘内注射NMDA可诱导脊髓后角HO-1蛋白表达增加。结论 NMDA受体激活可促进脊髓神经元HO-1蛋白的表达。     

实验性癫痫时大鼠海马内兴奋性氨基酸受体对内阿片肽含量的影响

应用免疫组织化学方法观察了青霉素致痫及海马内微量注射NMDA受体拮抗剂MK801（5－methy1－10，11－dihydro－5H－dibenzo[a，d]cycloheptan－5，10－iminemaleate)和非NMDA受体拮抗剂DNQX（6，7－dinitroquinoxaline－2，3－dione）后，大鼠海马内强啡肽A1~17和亮啡肽的含量变化。结果发现：在青霉素致痫4h后，海马苔样纤维和门区强啡肽A1~17的含量明显减少，海马CA1区．苔样纤维和门区的亮啡肽含量明显增加。在青霉素致痫前分别在海马内微量注射MK801（6μg）和DNQX（4μg），则在癫痫发作减弱同时，海马内强啡肽A1~17含量较单纯青霉素致痫组增加，亮啡肽含量下降。结果提示：青霉素致痫引起大鼠脑内强啡肽A1~17和亮啡肽含量变化，可能和NMDA受体和非NMDA受体的参与有关。     

疼痛及针刺镇痛时孤啡呔受体mRNA的变化

目的：观察大鼠在福尔马林致痛及针刺镇痛时孤啡肽受体mRNA在一些与镇痛有关核团的变化情况。方法：采用原位杂交组织化学技术。结果：电地后10h，导水管周围腹侧区，中缝背核及中缝大核内孤啡肽受体mRNA阳性神经元数增多；而在大鼠脚掌注射福尔马林后，上述核团内孤啡肽受体mRNA阳性神经元数却明显减少，电针并注射福尔马林，脑内孤啡肽受体mRNA水平介于单用电针和福尔马林之间。结论：电针能促进孤啡肽受体的合成而伤害性刺激抑制啡肽受体的合成。     

MEK阻滞剂U0126对背根神经节压迫神经痛模型大鼠nNOS表达的影响

摘要 背景：胞外信号调节激酶（ERK）信号通路以及NO激活,是伤害性刺激引起中枢敏化和长时程神经元可塑性中的重要因素,但二者在慢性压迫性损伤引起的神经痛的形成和维持中的作用尚未见报道。 目的：研究ERK信号传导通路阻滞剂U0126对背根神经节压迫神经痛大鼠脊髓背角内神经型一氧化氮合酶表达。 设计,时间及地点：随机对照的实验研究,于2008年7月至2009年3月在吉林大学第一医院耳鼻咽喉头颈外科研究所完成。 材料：雄性Wistar大鼠由吉林大学实验动物中心提供;U0216（美国Bio-Mol公司产品） 方法：CCD模型建立后第五天,采用单次鞘内注射方法行U0126注射,同时在对照组给予鞘内注射无菌的5%二甲基亚砜。 主要观察指标：采用von Frey纤维丝和热痛刺激仪观察CCD大鼠鞘内应用U0126后机械性痛敏和热痛敏阈值的变化,同时应用免疫荧光染色和免疫印记方法观察其对大鼠脊髓背角内nNOS活性的影响。 结果：CCD引起大鼠脊髓背角内nNOS活性的增强,鞘内注射U0126抑制nNOS活性的同时能明显减轻由CCD导致的大鼠机械性痛敏和热痛敏。 结论：脊髓背角神经元胞内ERK信号通路活性的变化能够影响脊髓背角内nNOS表达,ERK参与介导了NO在神经病理性疼痛中的作用。。 主题词：细胞外信号调节激酶;一氧化氮合成酶;神经痛;中枢敏化;痛觉过敏     

谷氨酸对丘脑束旁核痛兴奋神经元放电的影响

目的：观察脑室注射谷氨酸（Glu)对大鼠丘脑束旁核（PF）痛兴奋神经元（PEN）电变化的影响。方法：以电脉冲刺激右侧坐骨神经作为伤害性痛刺激，用玻璃微电极细胞外记录神经元放电的变化。结果：（1）伤害性刺激使大鼠丘脑PF的PEN诱发放电频率增加；（2）脑室注射Glu(1.5μg/10μl）加强PEN的电活动，使PEN放电频率的净增值增加，潜伏期缩短；（3）这种作用可被Glu的NMDA受体拮抗剂MK－801（0．17μg/0.5μl)所阻断。结论：Glu在中枢痛沉调制中可能起兴奋作用，而NMDA受体参与介导中枢伤害性信息的传递过程。     

脊髓神经元凋亡在鞘内注射血小板活化因子诱发大鼠痛敏中的作用

目的：探讨脊髓神经元凋亡在鞘内注射血小板活化因子（PAF）诱发大鼠痛敏中的作用。方法鞘内置管成功的雄性 Sprague-Dawley 大鼠60只,随机分为2组：对照组,30只,鞘内注射人工脑脊液（arti-ficial cerebral spinal fluid,ACSF）10μl;PAF 组,30只,鞘内注射 PAF 10μg,溶解于10μl 人工脑脊液;分别于鞘内给药前1 d、给药后1、3、5、7、14 d 分别测定机械痛阈（PWMT）和热痛阈（PWTL）。取 L4-6脊髓,采用TUNEL 法观察脊髓神经元凋亡。结果鞘内注射血小板活化因子（PAF）可诱发出大鼠机械性触诱发痛和热痛觉过敏。PAF 组术后1 d 脊髓中开始有少量凋亡神经元出现,凋亡指数于术后3 d 开始迅速增加,术后5 d 达峰值,与对照组比较,有显著性差异（P 〈0.01）。结论鞘内注射 PAF 诱发大鼠触觉异常痛敏和热痛敏,脊髓神经元凋亡可能参与了鞘内注射 PAF 大鼠痛敏的形成。     

中脑导水管周围灰质和海马在ACTH镇痛中的相互关系

以往工作发现，中脑导水管周围灰质（ＰＡＧ）和海马在非阿片肽ＡＣＴＨ痛觉调制中占有重要地位。但它们之间的相互影响在ＡＣＴＨ痛觉调制中的作用，尚未阐明。本工作利用免疫组织化学和病阈测定方法，进一步观察大鼠ＰＡＧ和海马在ＡＣＴＨ镇痛时的相互关系，并与吗啡镇痛作用相比较。结果如下：（１）海马内注射ＡＣＩＨ（０．５ｕ／４μｌ）或吗啡（５μｇ／４μｌ），痛阈明显升高（１１９．３±４．７％，１２２．７±２６．８％）与对照组比较有显著差异（Ｐ＜０．０１），该明显效应均可被ＰＡＧ内注射阿片受体拮抗剂纳络酮所阻断；（２）ＰＡＧ内注射吗啡或ＡＣＴＨ后病阈提高更显著（１８０．９±５０．３％，２１９．８±７７．０％，Ｐ＜０．０１），但海马内注射纳络酮可阻断前者的效应（Ｐ＜０．０５）而对后者却无影响（Ｐ＞０．０５）；（３）伤害性刺激福尔马林（Ｆ）可诱发大鼠脊髓腰膨大背角原癌基因ｃ－ｆｏｓ显著表达，以Ⅰ、Ⅱ层较显著，海马或ＰＡＧ内注射ＡＣＴＨ均可抑制其背角ｃ－ｆｏｓ表达。结果提示：ＰＡＧ、海马均参与ＡＣＴＨ和阿片系统对脊髓痛信息传递的调制作用，在ＡＣＴＨ痛觉调制作用中，表明ＰＡＧ、海马之间的相互影响是复杂的。     

骨癌痛大鼠脊髓背角Nogo-A 及其受体NgR1表达的变化

目的 观察骨癌痛大鼠脊髓背角Nogo-A 及其受体NgR1 表达的变化。方法 雌性未交 配SD 大鼠60 只,体重160～200 g,采用随机数字表法将其分为两组（n=30）：假手术组（S 组）和骨癌痛组 （BCP组）。BCP组于左侧胫骨骨髓腔内注射5 μl Walker256 乳腺癌细胞制备骨癌痛模型,S 组左侧胫骨 骨髓腔内注射生理盐水5 μl。选用von Frey 纤维丝检测各组大鼠造模前1 d 及造模后3、7、14、21 d 机 械缩足阈值（MWT）,评价疼痛行为学变化。于造模后7、14、21 d痛阈测定后取大鼠L 4～5脊髓背角,采 用Western Blot法测定 Nogo-A及其受体NgR1的表达。结果 与S组比较,BCP组肿瘤细胞接种后第7 天 MWT［（3.63±1.61）g］、第14天MWT［ （2.53±1.39）g］、第21天MWT［（2.40±1.16）g］降低（P＜0.05）;与 S 组比较,BCP 组大鼠术后7、14、21 d 脊髓背角Nogo-A 及其受体NgR1 表达上调（P＜ 0.05）。结论 脊髓 背角Nogo-A 及其受体NgR1 可能参与了骨癌痛机械痛敏的形成。     

抗精神病药物对精神分裂症大鼠模型痛阈和运动行为的影响

背景既往研究提示精神分裂症患者的疼痛敏感性降低并且可以被抗精神病药物部分逆转。对这一假说的评价方法之一是检测精神分裂症模型。目的在显示出预期的行为学改变的氯胺酮诱导的精神分裂症大鼠模型中,检测是否出现痛闾升高,并且检测抗精神病药物预处理是否逆转这种痛阈升高。方法将30只雄性Wistar大鼠随机分为5组,其中3组先腹腔注射抗精神病药物预处理[利培N（o．3mg,／kg）、利培酮（0．9mg／kg）或氟哌啶醇（1mg／kg）],30min后再腹腔注射氯胺酮（100mg／kg）;1组先腹腔注射生理盐水,再腹腔注射氯胺酮;1个对照组接受2次生理盐水注射。测定大鼠在基线以及第二次注射后第5、15、30和45min的压痛和热痛阈值。另外的30只大鼠做同样处理,用旷场实验观测大鼠在第二次注射后120min内的行为改变。结果与对照组相比,在所有时间段内,氯胺酮组大鼠（未用抗精神病药物）出现压痛阈降低、热痛阈升高。在所有时间段内,氟哌啶醇预处理明显减轻了氯胺酮诱导的压痛降低,但高或低剂量的利培酮对压痛阈无明显影响。用低剂量利培酮预处理减轻了氯胺酮诱导的第5min时段的热痛阈升高,但不包括第15—45min时段。高剂量利培酮和氟哌啶醇对热痛阈无明显影响。在旷场实验中,抗精神病药物预处理的各组比仅用氯胺酮处理的一组有较少的直立行为（目标指向的行为）,较少的穿越格子行为（较低的高运动性）,较少的摇头和转圈运动。氟哌啶醇预处理组比氯胺酮组（无预处理）和2个利培酮预处理组相比,摔倒（即共济失调）更为常见。结论我们不能肯定先前所见的在精神分裂症大鼠模型中抗精神病药物对氯胺酮诱导的痛阈升高有抑制作用。氯胺酮引起的压痛阈明显降低可能与氯胺酮注射后增强的全身活动性有关（这使压痛阈检测难以可靠进行）。利培酮和氟哌啶醇有效减轻多方面的氯胺酮引起的拟精神病症状,而氟哌啶醇增强了氯胺酮引起的共济失调,利培酮降低了共济失调。这一资料与易于摔倒的老年患者有临床相关性。     

Coexpression of lactosyl and gangliotetraosyl gangliosides in rat cerebellar radial glial cells in culture

The expression of gangliosides of the lactosylceramide (LC) and of the gangliotetraosylceramide (GTC) series on the surface of cells from rat embryonic cerebellar tissue was investigated by double-color indirect immunofluorescence. GD3 was assumed to be representative of LC and was detected using a specific monoclonal antibody. GM1 was assumed to be representative of GTC and was detected using the binding of cholera toxin followed by the binding of cholera toxin antibodies. The expression of polysialosylated GTC (polysialosyl-GTC) was detected using the cholera toxin-cholera toxin antibody experimental approach after conversion of polysialosyl-GTC to GM1 by treatment of the cells with neuraminidase. To distinguish the major neural cell types present in the cultures the expression of the following cell type-specific markers was investigated: neuron-specific enolase and microtubule-associated protein-2 (MAP-2) as probes for neuronal cells and the intermediate filament protein glial fibrillar acidic protein (GFAP) as a probe for astroglial cells. More than 80% of cells dissociated from cerebellar tissue of 15-day-old rat embryos (E15) are positive for the expression of GD3 and about 50% for the expression of GM1 and polysialosyl-GTC, but most are negative for the expression of neuron-specific enolase, MAP-2, and GFAP. After culturing for 4 days (E15 + 4) most cells that show characteristics of neuronal cells are positive for the expression of polysialosyl-GTC and "inactivate" the expression of GD3. Most cells with characteristics of radial and stellate glial cells are also positive for the expression of polysialosyl-GTC, but unlike neuron-like cells, they do not "inactivate" the expression of GD3.     

The role of the androgen receptor in CNS masculinization

The medial posterior region of the bed nucleus of the stria terminalis (BSTMP) and the locus coeruleus (LC) show opposite patterns of sexual dimorphism. The BSTMP in males is greater in volume and number of neurons than in females (male > female) while in the LC, the opposite is true (female > male). To investigate the possible role of the androgen receptor (AR) in the masculinization of these two structures, males with the testicular feminization mutation (Tfm) were compared to their control littermate males. No differences were seen in the number of neurons of the BSTMP between Tfm and their control littermate males, while in the LC, Tfm males have a greater number of neurons than their control littermate males. These results show that the AR is involved in the control of neuron number in the LC but not in the BSTMP. Results based on the LC suggest that when females have a larger brain area than males, masculinization in males may be achieved through the AR, with androgens perhaps decreasing cell survival.     

Age-related changes in erythropoietin immunoreactivity in the cerebral cortex and hippocampus of rats

Although oxidative stress may influence the fluid properties of blood, resulting in a potential decrement in blood flow and oxygen delivery to the brain during aging, very little is known about age-related changes in Epo expression. Therefore, we examined age-related changes in Epo expression in the cerebral cortex and hippocampus with an immunohistochemical technique. In aged rats, there was a significant decrease in Epo immunoreactivity in the pyramidal cells in the cortical regions. In the hippocampus of adult rats, a distinct immunoreactivity pattern was observed in the CA1-3 areas and dentate gyrus. In aged hippocampus, Epo immunoreactivity was significantly deceased in the pyramidal layer of CA1 regions, and the granule cell layer of dentate gyrus. It was noted that there was distinct pattern of Epo immunoreactivity in the pyramidal layer of CA2-CA3 region of aged rats. Epo immunoreactivity was relatively strong, but was observed only in the periphery of the cytoplasm. The first demonstration of age-related decreases in Epo expression in the cerebral cortex and hippocampus may provide useful data for investigating the pathogenesis of age-related neurodegenerative diseases, suggesting that age-related decreases in Epo may contribute to degenerative events following age-related decreases in brain flow and oxygen supply.     

Dose-dependent reductions in spatial learning and synaptic function in the dentate gyrus of adult rats following developmental thyroid hormone insufficiency

Thyroid hormones are critical for the development and maturation of the central nervous system. Although somatic and neurological effects are well documented following severe thyroid hormone deprivation, much less is known of the functional consequences of moderate levels of hormone insufficiency. We have previously demonstrated that severe thyroid hormone reductions in the postnatal period are associated with impairments in synaptic transmission in the dentate gyrus. The present study was performed to examine the dose-response relationships of moderate levels of hormone disruption on synaptic function in the dentate gyrus in an in vivo preparation and to determine the effects on spatial learning. Pre- and postnatal thyroid hormone insufficiency was induced by administration of 3 or 10 ppm propylthiouracil (PTU) to pregnant and lactating dams via the drinking water from gestation day (GD) 6 until postnatal day (PN) 30. This regimen produced a 47% and 65% reduction in serum T4, in the dams of the low and high-dose groups, respectively. At the time of testing of adult offspring, hormone status had returned to control levels. In littermates, field potentials evoked in the dentate gyrus in response to stimulation of the perforant path were assessed under urethane anesthesia. The data reveal dose-dependent reductions in synaptic transmission and impairments in long-term potentiation (LTP) of the EPSP component of the compound field potential. In contrast, LTP of the population spike measure was paradoxically enhanced. Spatial learning in the Morris water maze was profoundly impaired in high-dose animals. Although the majority of subjects in the low-dose group eventually acquired the task, their acquisition rate lagged behind control values. Reversal learning was assessed in all animals reaching criterion performance and found to be impaired in PTU-exposed animals relative to controls. These data support previous findings in area CA1 in vitro, extend observations associated with dentate gyrus synaptic function to a lower dose range, and provide correlative evidence of behavioral disruption in a hippocampal-dependent learning task following developmental thyroid hormone insufficiency.     

唑吡坦治疗老年原发性失眠的开放性前瞻性多中心自身对照研究

Objective To evaluate the clinical efficacy and safety of zolpidem in treatment of primary insomnia in elderly patients.Methods An open, perspective, fixed-dose, multicentre and selfcontrolled clinical trial was conducted.Total of 115 elderly patients who met with the Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria for primary insomnia were administered 3 week nightly treatment with zolpidem 5 mg.The primary efficacy measurement was the change of Pittsburg Sleep Quality Index(PSQI) score after 1 week treatment in comparison with the baseline.The secondary efficacy measurement included the changes from baseline in total score of the PSQI, Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA) and self-reported sleeping parameters ( latency of falling asleep, total sleeping time and sleeping quality) after 3 week treatment.Results The mean reduction score 17 items of PSQI were 2.8 after 1 week treatment and 3.2 at the end of 3 week ( P ＜ 0.01 ).The selfreported sleeping parameters were much improved from the baseline (P ＜0.01 ).The total scores of HAMD and HAMA were reduced significantly ( P ＜ 0.01 ) after 3 week treatment.The overall incidence of adverse events was 19.1%, with the frequent adverse events of dizziness, headache, sleepiness, nausea and fatigue, and the severity was mild or moderate.Conclusion It is effective and safe of zolpidem 5 mg nightly in treatment of elderly insomnia patients.     

唑吡坦治疗老年原发性失眠的开放性前瞻性多中心自身对照研究

Objective To evaluate the clinical efficacy and safety of zolpidem in treatment of primary insomnia in elderly patients.Methods An open, perspective, fixed-dose, multicentre and selfcontrolled clinical trial was conducted.Total of 115 elderly patients who met with the Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria for primary insomnia were administered 3 week nightly treatment with zolpidem 5 mg.The primary efficacy measurement was the change of Pittsburg Sleep Quality Index(PSQI) score after 1 week treatment in comparison with the baseline.The secondary efficacy measurement included the changes from baseline in total score of the PSQI, Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA) and self-reported sleeping parameters ( latency of falling asleep, total sleeping time and sleeping quality) after 3 week treatment.Results The mean reduction score 17 items of PSQI were 2.8 after 1 week treatment and 3.2 at the end of 3 week ( P ＜ 0.01 ).The selfreported sleeping parameters were much improved from the baseline (P ＜0.01 ).The total scores of HAMD and HAMA were reduced significantly ( P ＜ 0.01 ) after 3 week treatment.The overall incidence of adverse events was 19.1%, with the frequent adverse events of dizziness, headache, sleepiness, nausea and fatigue, and the severity was mild or moderate.Conclusion It is effective and safe of zolpidem 5 mg nightly in treatment of elderly insomnia patients.     

Regulation of kinesin light chain 1 level correlates with the development of morphine reward in the mouse brain

Persistent changes that take place during the development of opioid addiction are thought to be due to reorganization of synaptic connections in relevant brain circuits. This neuronal plasticity requires trafficking of signaling molecules that are controlled by kinesins. In neurons, kinesin light chain 1 (KLC1) acts as the primary regulator of kinesin action. We observed that KLC1 was enriched in sub-cortical regions of the brain in C57Bl/6J mice. KLC1 expression was especially enriched in the striatum, hippocampus and amygdala, which are known to be involved in opioid addiction. Our study revealed that conditioning of C57Bl/6J mice with morphine elevated KLC1 levels in the amygdala, frontal cortex and hippocampus, but not in the striatum. Further study revealed that alterations in KLC1 protein levels in the studied brain regions correlated with the expression of morphine-induced conditioned place preference. In the cortex, hippocampus and amygdala, KLC1 co-localized with calcium/calmodulin-dependent protein kinase II (CaMKII), suggesting that KLC1 was present in the cell bodies and dendrites of pyramidal neurons. Our findings indicate that KLC1, a molecule involved in dendritic and axonal transport in the brain, is affected during chronic morphine treatment and may be involved in the development of opioid addiction.     

'Programming' of orexigenic and anorexigenic hypothalamic neurons in offspring of treated and untreated diabetic mother rats

Exposure to maternal diabetes in utero (GD) may 'program' for obesity. Orexigenic neuropeptides, like neuropeptide Y (NPY) and agouti-related peptide (AGRP), and anorexigenic neuropeptides, like proopiomelanocortin (POMC) and alpha-melanocyte-stimulating hormone (MSH), are decisively involved in body weight regulation. We investigated consequences of GD and its treatment by pancreatic islet transplantation in rats for development of neuropeptidergic neurons in the arcuate hypothalamic nucleus (ARC) in weanling offspring. In GD, islet transplantation on d15 of pregnancy led to normalized blood glucose. Sham-transplanted GD mothers (TSGD) remained hyperglycemic. Twenty-one-day-old TSGD offspring developed hypothalamic 'malorganization'. Despite of normal leptin and insulin levels in TSGD offspring, increased immunopositivity of NPY and AGRP appeared. TSGD offspring showed unchanged POMC, but decreased MSH-immunopositivity. In conclusion, untreated diabetes in pregnant rats leads to 'malprogramming' of hypothalamic neuropeptidergic neurons in offspring, probably contributing to later development of overweight. These acquired alterations are preventable by treatment of maternal GD.     

Effects of cannabis exposure in the prenatal and adolescent periods: Preclinical and clinical studies in both sexes

Cannabis is the most commonly used illicit drug among adolescents and young adults, including pregnant women. There is substantial evidence for a significant association between prenatal cannabis exposure and lower birth weight in offspring, and mixed results regarding later behavioural outcomes in the offspring. Adolescent cannabis use, especially heavy use, has been associated with altered executive function, depression, psychosis and use of other drugs later in life. Human studies have limitations due to several confounding factors and have provided scarce information about sex differences. In general, animal studies support behavioural alterations reported in humans and have revealed diverse sex differences and potential underlying mechanisms (altered mesolimbic dopaminergic and hippocampal glutamatergic systems and interference with prefrontal cortex maturation). More studies are needed that analyse sex and gender influences on cannabis-induced effects with great clinical relevance such as psychosis, cannabis use disorder and associated comorbidities, to achieve more personalized and accurate treatments.