Abstract
BackgroundMany studies have demonstrated that repeated injections of nicotine can produce progressive increases in locomotor activity and enhanced expression of c-fos and tyrosine hydroxylase (TH) in brain dopaminergic areas. Paecilomyces japonica (PJ) is a herbal medicine that is commonly used to treat opiate and other addictions in Eastern Asia. However, its influence on nicotine addiction has not been examined. This study was carried out to investigate the effects of PJ on repeated nicotine-induced behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry.MethodsRats were pretreated with PJ (10, 25, 50, 100, and 200 mg/kg, intraperitoneally) 30 min before repeated injections of nicotine (0.4 mg/kg, subcutaneously, twice daily for 7 days). Locomotor activity was measured in rats during 7-day nicotine treatments. On the seventh day, c-Fos and TH expression were assessed.ResultsPretreatment with PJ decreased the development of nicotine-induced sensitization, c-Fos expression in the nucleus accumbens and striatum, and TH expression in the ventral tegmental area. PJ decreased nicotine-induced locomotor activity by modulating brain dopaminergic systems.ConclusionThe results of the present study suggest that PJ may be a useful agent for preventing and treating nicotine addiction.
Highlights
Many studies have demonstrated that repeated injections of nicotine can produce progressive increases in locomotor activity and enhanced expression of c-fos and tyrosine hydroxylase (TH) in brain dopaminergic areas
A repeated-measures analysis of variance (7 × 8, treatment × time) performed on the locomotor activity following the Paecilomyces japonica (PJ) treatments for the development test indicated a significant effect of drug [F(6,40) = 28.240, p < 0.001], a significant effect of time [F(7,42) = 3.964, p < 0.001], and a significant interaction between drug × time [F(42,280) = 3.481, p < 0.001]
The present study demonstrated increased Fos-like immunoreactivity in the nucleus accumbens (NAc) and striatum and TH-like immnoreactivity in the ventral tegmental area (VTA), which are the major projection areas of the dopaminergic system
Summary
Many studies have demonstrated that repeated injections of nicotine can produce progressive increases in locomotor activity and enhanced expression of c-fos and tyrosine hydroxylase (TH) in brain dopaminergic areas. This study was carried out to investigate the effects of PJ on repeated nicotine-induced behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry. The World Health Organization reports that there are approximately 1.25 billion smokers worldwide at present and that global mortality because of tobacco-related diseases will likely increase from approximately five million deaths annually in 2004, to over ten million deaths per year in 2030 [2]. For these reasons, cigarette smoking is a massive health problem in the world. The mechanisms of behavioral sensitization have been suggested as an animal model of drug addiction mainly associated with repeated administration of psychomotor stimulant drugs, and it has been implicated in the development of drug addiction [8] and drug-induced psychosis [9, 10]
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