Aims: 

The chronic nicotine treatment induces hyperactivity, while the consecutive nicotine withdrawal elicits hypoactivity in mammals. Hyperactivity means hyperlocomotion and anxiogenesis, whereas hypoactivity denotes hypolocomotion and anxiolysis. These mechanisms are mediated probably via the striatum, amygdala and hypothalamus-hypophysis-adrenal cortex. In the present study we investigated the effect of the selective CRF1 receptor antagonist antalarmin on these systems in chronically nicotine-treated and acutely withdrawn rats.

Methods: 

2 mg/kg nicotine was injected intraperitoneally for 7 days, 4 times/day and 0.1 mg/2 ml antalarmin was administered intracerebroventricularly on the 8th and the 9th day's morning. The horizontal activity, the vertical activity and the total distance travelled were examined in an in vivo, open field based conducta system. The striatal dopamine, the amygdalar GABA release and the plasma corticostreone concentration were determined by an in vitro superfusion system and chemical fluorescent assay, respectively.

Results: 

The nicotine treatment enhanced the locomotor activity, striatal dopamine and amygdalar GABA release which were inhibited significantly by antalarmin. The nicotine withdrawal reduced the locomotor activity and the plasma cortiosterone level, which were antagonized significantly by antalarmin. However the changes of dopamine release from the striatum and the GABA release from the amygdala were insignificant at this time.

Conclusion: 

Our results suggest that antalarmin reduces the nicotine treatment induced hyperactivity, and ameliorates the nicotine withdrawal elicited hypoactivity.