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

Abstract

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 ⅐ kg Ϫ1 ⅐ d Ϫ1) 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. Key words: nicotine; constant infusion; striatal dopamine metabolism; limbic dopamine metabolism; Fos protein; desensitization; toleranceAcute nicotine enhances striatal and limbic dopamine (DA) turnover and metabolism (Nose and Takemoto, 1974;Haikala et al., 1986;Grenhoff and Svensson, 1988). Nicotine increases 3 H-DA release in vitro from striatal slices and synaptosomes (Westfall, 1974;Rapier et al., 1988;Grady et al., 1992) and from the nucleus accumbens (NAcc) (Rowell et al., 1987). Nicotine also elevates extracellular DA in the striatum (Imperato et al., 1986) and in the NAcc (Imperato et al., 1986;Benwell and Balfour, 1992). There is evidence that nicotine activates the limbic DA system more easily than the striatal one (Imperato et al., 1986;Grenhoff and Svensson, 1988;Benwell and Balfour, 1997). We recently found that in mice tolerance develops to the nicotine-induced increase of striatal dopamine metabolism at 24 hr after withdrawal from 7 week oral nicotine administration (Pietilä et al., 1996). The effect of chronic nicotine treatment seems to depend on the method of administration. During prolonged constant nicotine infusion the acute nicotine-evoked increase of extracellular DA in the NAcc and dorsal striatum was inhibited, and the elevation of acc...

L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway

“…The expression of c-Fos increased significantly in the reward circuit-related areas after acute treatment with nicotine [35,36]. Moreover, the expression of c-Fos increased significantly in the NAc after nicotine was injected into the VTA directly [26].…”

Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

“…Regulation of neurotransmitter release The activation of nAChRs can influence gene expression for immediate early genes and genes involved in transmitter synthesis [15,52,59,60] . In the chick ciliary ganglion [61] , the nAChR-mediated control of transcription relies on calcium influx and calcium release from internal stores to activate first CaMKII/IV, and then ERK/MAPK.…”

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

“…Nicotinic transmission can also influence gene expression as originally shown for immediate early genes and genes involved in transmitter synthesis (Chalazonitis and Zigmond, 1980;Greenberg et al, 1986;Pelto-Huikko et al, 1995;Salminen et al, 1999;Gueorguiev et al, 2000). The underlying mechanisms have been examined in some detail in the chick ciliary ganglion .…”