[Neurochemical mechanisms for development of psychological dependence on volatile organic solvents].
Abuse of volatile organic solvents among youth remains a major social problem. Organic solvents are cheap and relatively easy to obtain, so they carry the risk of becoming a "gateway drug" for users. The effect of repeated inhalation of toluene on subsequent responses to other drugs of abuse is unclear. In the present study, we investigated the effect of toluene inhalation on methamphetamine-induced behavioral change using a newly developed sealed inhalation shuttlebox. The influence of the cyclic AMP response element binding (CREB) protein expression following toluene inhalation was also examined. Mice were exposed to toluene or air once daily for five days. Methamphetamine produced significant hyperlocomotion in air-exposed mice. This stimulatory effect of methamphetamine was significantly enhanced following repeated inhalation of toluene. Furthermore, repeated toluene inhalation increased the levels of CREB proteins in the limbic forebrain. The present study demonstrated that adaptation of the adenylate cyclase system following repeated toluene inhalation might be involved in the expression of behavioral sensitization to subsequent methamphetamine administration. Inhalant abuse could thus be associated with the risk of other substances of abuse.
Funada
Masahiko
M
Department of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo, 187-8553 Japan. mfunada@ncnp.go.jp
Aoo
Naoya
N
Wada
Kiyoshi
K
D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004357:Drug Synergism; D008032:Limbic System / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D012997:Solvents / Q000009:adverse effects*; D019966:Substance-Related Disorders / Q000209:etiology*; D014050:Toluene / Q000009:adverse effects; D014835:Volatilization
D017362:Cyclic AMP Response Element-Binding Protein; D012997:Solvents; D014050:Toluene; D008694:Methamphetamine; D000262:Adenylyl Cyclases