Futuristic Environmental Simulation Center, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
Curr Neuropharmacol. 2011 Mar;9(1):109-12. doi: 10.2174/157015911795016976.
Methamphetamine (METH) is a highly addictive drug, and addiction to METH has increased to epidemic proportions worldwide. Chronic use of METH causes psychiatric symptoms, such as hallucinations and delusions, and long-term cognitive deficits, which are indistinguishable from paranoid schizophrenia. The GABA receptor system is known to play a significant role in modulating the dopaminergic neuronal system, which is related to behavioral changes induced by drug abuse. However, few studies have investigated the effects of GABA receptor agonists on cognitive deficits induced by METH. In the present review, we show that baclofen, a GABA receptor agonist, is effective in treating METH-induced impairment of object recognition memory and prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating in mice. Acute and repeated treatment with METH induced a significant impairment of PPI. Furthermore, repeated but not acute treatment of METH resulted in a long-lasting deficit of object recognition memory. Baclofen, a GABA(B) receptor agonist, dose-dependently ameliorated the METH-induced PPI deficits and object recognition memory impairment in mice. On the other hand, THIP, a GABA(A) receptor agonist, had no effect on METH-induced cognitive deficits. These results suggest that GABA(B) receptors may constitute a putative new target in treating cognitive deficits in chronic METH users.
甲基苯丙胺（METH）是一种高度成瘾的毒品，全球范围内对 METH 的成瘾已达到流行程度。慢性使用 METH 会导致精神病症状，如幻觉和妄想，以及长期认知缺陷，这与偏执型精神分裂症无法区分。众所周知，GABA 受体系统在调节多巴胺能神经元系统方面发挥着重要作用，而后者与滥用药物引起的行为变化有关。然而，很少有研究调查 GABA 受体激动剂对 METH 引起的认知缺陷的影响。在本综述中，我们表明，GABA 受体激动剂巴氯芬可有效治疗 METH 诱导的物体识别记忆和起始反射的前脉冲抑制（PPI）损伤，这是一种用于测量感觉运动门控的方法在小鼠中。急性和重复使用 METH 会导致 PPI 显著受损。此外，重复使用 METH 而不是急性使用 METH 会导致物体识别记忆的长期缺陷。GABA(B)受体激动剂巴氯芬可剂量依赖性改善 METH 诱导的 PPI 缺陷和小鼠的物体识别记忆损伤。另一方面，GABA(A)受体激动剂 THIP 对 METH 引起的认知缺陷没有影响。这些结果表明，GABA(B)受体可能成为治疗慢性 METH 使用者认知缺陷的新靶标。
