Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice.
Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-d-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure.
Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.
Ming-Huan
MH
Chan
Shiang-Sheng
SS
Chung
Astrid K
AK
Stoker
Athina
A
Markou
Hwei-Hsien
HH
Chen
D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D007035:Hypothermia / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D012521:Sarcosine / Q000494:pharmacology*; D012653:Self Stimulation / Q000502:physiology; D014050:Toluene / Q000633:toxicity*
D016194:Receptors, N-Methyl-D-Aspartate; D014050:Toluene; D012521:Sarcosine