The effects of acute
nicotine (0.5 mg/kg, s.c.) on
dopamine (DA) metabolism and Fos
protein expression in striatal and limbic areas of rats on the seventh day of chronic
nicotine infusion (4 mg. kg(-1). d(-1)) and after 24 or 72 hr withdrawal were investigated. In saline-infused rats, acute
nicotine elevated striatal and limbic
3,4-dihydroxyphenylacetic acid (
DOPAC) and
homovanillic acid (HVA) concentrations significantly. During the
nicotine infusion, no such increases were seen in the striatum, but limbic HVA was somewhat elevated. After 24 hr withdrawal when no
nicotine was found in the plasma, acute
nicotine elevated striatal
DOPAC and HVA and limbic HVA. However, the limbic
DOPAC was unaffected. Acute
nicotine increased Fos immunostaining (IS) in the caudate-putamen (CPU), the core of nucleus accumbens (NAcc), the cingulate cortex (Cg), and the central nucleus of amygdala (ACe) significantly. During
nicotine infusion the
nicotine-induced responses were attenuated in CPU and NAcc, whereas in ACe and Cg Fos immunostaining was increased as in saline-infused rats. After 24 hr withdrawal, acute
nicotine did not increase Fos immunostaining in CPU, NAcc, and Cg, but increased it clearly in ACe. After 72 hr withdrawal,
nicotine's effects were restored. Our findings suggest that the
nicotinic receptors in the striatal areas are desensitized more easily than those in the limbic areas. Furthermore, the effects of
nicotine on various DA metabolites differ. We also found evidence for long-lasting inactivation of
nicotinic receptors in vivo regulating limbic
dopamine metabolism and Fos expression in striatal and limbic areas. These findings might be important for the protective effects of
nicotine in
Parkinson's disease and in its dependence-producing properties.