期刊
CURRENT NEUROPHARMACOLOGY
卷 9, 期 1, 页码 109-112出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/157015911795016976
关键词
Baclofen; methamphetamine; cognition; prepulse inhibition; GABA(B) receptor
资金
- Japan Society for the Promotion of Science [19390062]
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Academic Frontier Project for Private Universities
- MEXT
- Ministry of Health, Labour and Welfare
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- JST, CREST
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.
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