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Pregabalin: Potential for Addiction and a Possible Glutamatergic Mechanism

机译：Pragabalin：成瘾潜力和可能的谷氨酸剂

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Drug addiction remains a prevalent and fatal disease worldwide that carries significant social and economic impacts. Recent reports suggest illicit pregabalin (Lyrica) use may be increasing among youth, however the addictive potential of pregabalin has not been well established. Drug seeking behavior and chronic drug use are associated with deficits in glutamate clearance and activation of postsynaptic glutamatergic receptors. In the current study, we investigated the abuse potential of pregabalin using conditioned place preference (CPP) paradigm. Different doses of pregabalin (30, 60, 90, and 120?mg/kg) were used to assess the seeking behavior in mice. Glutamate homeostasis is maintained by glutamate transporter type-1 (GLT-1), which plays a vital role in clearing the released glutamate from synapses and drug seeking behavior. Therefore, we investigated the role of glutamate in pregabalin-seeking behavior with ceftriaxone (CEF), a potent GLT-1 upregulator. Mice treated with pregabalin 60 and 90?mg/kg doses demonstrated drug seeking-like behavior, which was significantly blocked by CEF pretreatment. These results suggest that pregabalin-induced CPP was successfully modulated by CEF which could serve as a lead compound for developing treatment for pregabalin abuse.
机译：吸毒成瘾仍然是全世界患有显着的社会和经济影响的普遍性和致命的疾病。最近的报道表明非法普瑞巴林（Lyrica）在青年之间可能会增加，但普瑞巴林的上瘾潜力尚未得到很好的成熟。寻求药物寻求行为和慢性药物使用与谷氨酸间隙的缺陷有关，突触后谷氨酸受体的活化。在目前的研究中，我们研究了使用条件的地方偏好（CPP）范式的PREGABALIN的滥用潜力。使用不同剂量的普瑞巴林（30,60,90和120×mg / kg）来评估小鼠的寻求行为。谷氨酸稳态由谷氨酸转运蛋白类型-1（GLT-1）保持，这在清除突出的谷氨酸和药物寻求行为中起着至关重要的作用。因此，我们调查了谷氨酸在普瑞巴林寻求与头孢曲松（CEF）中的作用，有效的GLT-1上调器。用Praetabalin 60和90〜90？Mg / kg剂量治疗的小鼠显示出药物寻求类似的行为，其被CEF预处理显着堵塞。这些结果表明，普瑞巴林诱导的CPP通过CEF成功调节，其可以用作铅化合物，用于制定普瑞巴林滥用症的治疗。

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