Study of neuroadaptive mechanisms for development of psychological dependence on volatile organic solvents.

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Toluene and many toluene-containing products are abused via inhalation. A conditioning paradigm of toluene inhalation was developed in order to estimate the rewarding effect in mice. Toluene inhalation (700-3200ppm) produced a significant conditioned place preference in mice. These rewarding effects of toluene were abolished by pretreatment with dopamine D1 receptor antagonist SCH23390. Toluene inhalation significantly increased the dopamine level in the limbic forebrain (nucleus accumbens and olfactory tubercle). In contrast, toluene inhalation significantly decreased the dopamine metabolite (3,4-dihydroxyphenylacetic acid) level in the limbic forebrain. These results suggest that the conditioned place preference procedure using a newly developed novel sealed inhalation shuttlebox offers an important tool for studying the rewarding effect of abused solvents. Furthermore, the activation of D1 receptors may play an important role in the expression of the toluene-induced rewarding effect … More s. Toluene inhalation could activate the function of the mesolimbic dopamine system. Modification of the mesolimbic dopamine system may be involved in the expression of toluene-induced rewarding effect in mice. Furthermore, the effect of toluene inhalation on c-Fos protein expression in the brain to identify the most sensitive anatomical substrates for toluene inhalation was investigated. The influences of the cyclic AMP level and the cyclic AMP response element binding (CREB) protein expression were also examined. After toluene inhalation, the expression of c-Fos protein was found to have selectively increased in the limbic forebrain and the hippocampus, indicating that these brain regions may be anatomical substrates for toluene inhalation. Furthermore, repeated toluene inhalation increased the levels of cAMP and phospho-CREBproteins in the limbic forebrain. These results suggest that adaptation of the adenylyl cyclase system after repeated toluene inhalation may play an important role in the development of the rewarding effect of toluene. Less