[In vitro assessment of neuropsychotoxicity of abused drugs using organotypic slice cultures].
Repeated, intermittent administration of abused drugs such as psychostimulants, opioids and some recreational drugs causes progressive augmentation of their locomotor response. This phenomenon, termed behavioral sensitization, is thought to underlie certain aspects of drug addiction. It is well established that the behavioral sensitization is based on the augmentation of the mesocorticolimbic dopaminergic activity originating in the ventral tegmental area of the midbrain that project to the nucleus accumbens, the medial prefrontal cortex and other forebrain regions. In addition to the dopaminergic system, recent evidence suggests the involvement of the raphe serotonergic neurons in drug addiction. Many studies for drug addiction have been assessed by in vivo experiments in whole animals, because these addiction-related phenomena are thought to be due to long-term alterations of psychological behavior based on plasticity of neural circuits. Nevertheless, in vitro model systems that retain neuronal and synaptic function and is available for long-term analysis, should provide a great deal of experimental access to evaluate neural plasticity underlying drug addiction. However, no reports have successfully analyzed the altered dopaminergic and serotonergic activities following long-term exposure to abused drugs using in vitro model system. In this mini-review, our recent in vitro studies on the abused drug-induced neural adaptation of the mesocorticolimbic dopaminergic and the raphe serotonergic neurons using rat organotypic slice cultures are introduced.
Nakagawa
Takayuki
T
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Kaneko
Shuji
S
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects*; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D019966:Substance-Related Disorders / Q000503:physiopathology*