摘要
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-HT_(2A))受体拮抗剂凯坦色林1.0 mg·kg^(-1),DOM 3.0 mg·kg^(-1)+5-HT_(2C)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-HT_(2A)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)+SB2420843.0 mg·kg^(-1),ketanserin 1.0 mg·kg^(-1),SB2420843.0 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 lowγoscillations(P<0.05,P<0.01)in OFC compared to saline.Ketanserin(1.0 mg·kg^(-1))antagonized DOM induced changes in lowγoscilla-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 lowγoscillations and increase of HFO in OFC by acting at 5-HT_(2A) receptors.
作者
王妍
江凯丽
刘晓燕
苏瑞斌
WANGYan;JIANG Kaili;LIUXiaoyan;SURuibin(Nanjing University of Chinese Medicine,Nanjing 210000,China;State Key Laboratory of National Security Specially Needed Medicines,Academy of Military Medical Sciences,Beijing 100850,China)
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2024年第5期335-343,共9页
Chinese Journal of Pharmacology and Toxicology
关键词
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
hallucinogens
2,5-dimethoxy-4-methylamphetamine
orbitofrontal cortex
local field potentials
γoscillations
high frequency oscillations
