Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain.
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain.
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DOI：
10.3389/fphar.2014.00010
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发表时间：
2014
影响因子：
5.6
通讯作者：
Abílio VC
中科院分区：
文献类型：
--
作者：
Levin R;Peres FF;Almeida V;Calzavara MB;Zuardi AW;Hallak JE;Crippa JA;Abílio VC
临床和神经生物学研究结果表明，大麻素和内源性大麻素系统可能与精神分裂症的病理生理和治疗有关。我们描述了自发性高血压大鼠（SHR）株表现出一种精神分裂症行为表型，这种表型被抗精神病药物特异性地减弱，并被精神分裂症前操作增强。基于这些发现，我们建议该菌株作为精神分裂症的动物模型。本研究的目的是评估大麻素类药物对惊吓前脉冲抑制（PPI）缺陷的影响，这是研究精神分裂症相关感觉运动门控障碍的主要范式，由SHR菌株提出。使用以下药物：(1)win55212,2（大麻素激动剂），(2)利莫那班（CB1拮抗剂），(3)AM404（阿南胺摄取抑制剂），(4)大麻二酚（CBD；间接CB1/CB2受体拮抗剂，以及其他作用）。Wistar大鼠（WRs）和SHRs分别用载药（VEH）或不同剂量的WIN55212（0.3、1或3 mg/kg）、利莫那班（0.75、1.5或3 mg/kg）、AM404（1、5或10 mg/kg）或CBD（15、30或60 mg/kg）处理。与WRs相比，veh处理的SHRs PPI下降。1 mg/kg WIN和30 mg/kg CBD可以逆转这种PPI缺陷。相反，0.75 mg/kg利莫那班降低了SHR菌株的PPI，而AM404对其没有影响。我们的研究结果加强了内源性大麻素系统在精神分裂症相关的感觉运动门控障碍中的作用，并指出大麻素药物是潜在的治疗策略。
Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia. We described that the spontaneously hypertensive rats (SHR) strain presents a schizophrenia behavioral phenotype that is specifically attenuated by antipsychotic drugs, and potentiated by proschizophrenia manipulations. Based on these findings, we have suggested this strain as an animal model of schizophrenia. The aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition (PPI) of startle, the main paradigm used to study sensorimotor gating impairment related to schizophrenia, presented by the SHR strain. The following drugs were used: (1) WIN55212,2 (cannabinoid agonist), (2) rimonabant (CB1 antagonist), (3) AM404 (anandamide uptake inhibitor), and (4) cannabidiol (CBD; indirect CB1/CB2 receptor antagonist, among other effects). Wistar rats (WRs) and SHRs were treated with vehicle (VEH) or different doses of WIN55212 (0.3, 1, or 3 mg/kg), rimonabant (0.75, 1.5, or 3 mg/kg), AM404 (1, 5, or 10 mg/kg), or CBD (15, 30, or 60 mg/kg). VEH-treated SHRs showed a decreased PPI when compared to WRs. This PPI deficit was reversed by 1 mg/kg WIN and 30 mg/kg CBD. Conversely, 0.75 mg/kg rimonabant decreased PPI in SHR strain, whereas AM404 did not modify it. Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.
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DOI：
10.1007/s00406-009-0024-2
发表时间：
2009-10
影响因子：
4.7
作者：
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通讯作者：
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