The effects of acute nicotine on the metabolism of dopamine and the expression of Fos protein in striatal and limbic brain areas of rats during chronic nicotine infusion and its withdrawal
O. Salminen et al., The effects of acute nicotine on the metabolism of dopamine and the expression of Fos protein in striatal and limbic brain areas of rats during chronic nicotine infusion and its withdrawal, J NEUROSC, 19(18), 1999, pp. 8145-8151
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 sev
enth 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 nicoti
ne elevated striatal and limbic 3,4-dihydroxyphenylacetic acid (DOPAC) and
homovanillic acid (HVA) concentrations significantly. During the nicotine i
nfusion, no such increases were seen in the striatum, but limbic HVA was so
mewhat elevated. After 24 hr withdrawal when no nicotine was found in the p
lasma, acute nicotine elevated striatal DOPAC and HVA and limbic HVA. Howev
er, the limbic DOPAC was unaffected. Acute nicotine increased Fos immunosta
ining (IS) in the caudate-putamen (CPU), the core of nucleus accumbens (NAc
c), the cingulate cortex (Cg), and the central nucleus of amygdala (ACe) si
gnificantly. During nicotine infusion the nicotine-induced responses were a
ttenuated in CPU and NAcc, whereas in ACe and Cg Fos immunostaining was inc
reased as in saline-infused rats. After 24 hr withdrawal, acute nicotine di
d not increase Fos immunostaining in CPU, NAcc, and Cg, but increased it cl
early in ACe. After 72 hr withdrawal, nicotine's effects were restored. Our
findings suggest that the nicotinic receptors in the striatal areas are de
sensitized more easily than those in the limbic areas. Furthermore, the eff
ects of nicotine on various DA metabolites differ. We also found evidence f
or long-lasting inactivation of nicotinic receptors in vivo regulating limb
ic dopamine metabolism and Fos expression in striatal and limbic areas. The
se findings might be important for the protective effects of nicotine in Pa
rkinson's disease and in its dependence-producing properties.