2,5-二甲氧基-4-甲基苯丙胺对大鼠眶额叶皮质低γ和高频振荡的影响OA北大核心CSTPCD
Effect of 2,5-dimethoxy-4-methylamphetamine on low γ and high-frequency oscillations in rat orbitofrontal cortex
目的 探究经典致幻剂2,5-二甲氧基-4-甲基苯丙胺(DOM)致精神障碍的潜在电生理机制.方法 对成年雄性SD大鼠进行眶额叶皮质(OFC)微丝电极阵列植入手术,术后恢复1周,采用自身对照按以下给药顺序依次ip给药:DOM(0.5,1.5和3.0 mg·kg-1),DOM 3.0 mg·kg-1+5-羟色胺2A(5-HT2A)受体拮抗剂凯坦色林1.0 mg·kg-1,DOM 3.0 mg·kg-1+5-HT2C受体拮抗剂SB242084 3.0 mg·kg-1,凯坦色林 1.0 mg·kg-1,SB242084 3.0 mg·kg-1.每次药物处理前ip给予生理盐水作为对照组.每次药物处理间隔洗脱期1周.用Plexon在体多通道记录系统记录大鼠OFC脑区场电位,分析给药前后大鼠场电位变化.结果 与对照组相比,DOM(0.5,1.5和3.0 mg·kg-1)能够增加OFC脑区高频振荡(HFO)功率(P<0.05),降低低γ振荡功率(P<0.05,P<0.01);凯坦色林1.0 mg·kg-1能够拮抗DOM引起的低γ(P<0.01)和HFO(P<0.05)功率的变化,SB242084 3.0 mg·kg-1无拮抗作用.结论 DOM引起的幻觉等精神神经系统障碍可能与5-HT2A受体介导的OFC脑区低γ振荡功率降低和HFO功率增加有关.
OBJECTIVE To investigate possible electrophysiological mechanisms of psychogenic disorders caused by the classical hallucinogen 2,5-dimethoxy-4-methylamphetamine(DOM).METHODS Microelectrode array implantation in the orbitofrontal cortex(OFC)was performed in adult male SD rats.After one week of recovery from surgery,the drugs were administered intraperitoneally to rats in the following order:DOM(0.5,1.5,and 3.0 mg·kg-1),DOM 3.0 mg·kg-1+ketanserin 1.0 mg·kg-1,DOM 3.0 mg·kg-1+SB242084 3.0 mg·kg-1,ketanserin 1.0 mg·kg-1,SB242084 3.0 mg·kg-1.Saline was given as a control group before each drug treatment.The changes of field potential(LFP)in OFC were recorded by the Plexon in vivo multichannel recording system.There was one week of washout of drugs between medications.RESULTS DOM(0.5,1.5 and 3.0 mg·kg-1)increased the power of high frequency oscillations(HFO,P<0.05)but decreased the power of low γ oscillations(P<0.05,P<0.01)in OFC compared to saline.Ketanserin(1.0 mg·kg-1)antagonized DOM induced changes in low γ oscilla-tions(P<0.01)and HFO(P<0.05)power,but SB242084(3.0 mg·kg-1)did not.CONCLUSION DOM can cause such psychoneurological disorders as hallucinations,which may be related to the power decrease of low γ oscillations and increase of HFO in OFC by acting at 5-HT2A receptors.
王妍;江凯丽;刘晓燕;苏瑞斌
南京中医药大学,江苏 南京 210000||军事科学院军事医学研究院国家安全特需药品全国重点实验室,北京 100850军事科学院军事医学研究院国家安全特需药品全国重点实验室,北京 100850
药学
致幻剂2,5-二甲氧基-4-甲基苯丙胺眶额叶皮质局部场电位γ振荡高频振荡
hallucinogens2,5-dimethoxy-4-methylamphetamineorbitofrontal cortexlocal field potentialsγ oscillationshigh frequency oscillations
《中国药理学与毒理学杂志》 2024 (005)
335-343 / 9
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