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The Journal of Neuroscience, September 15, 1999, 19(18):8145-8151

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

Outi Salminen, Tiina Seppä, Helena Gäddnäs, and Liisa Ahtee

Division of Pharmacology and Toxicology, Department of Pharmacy, University of Helsinki, FIN-00014 Helsinki, Finland

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 · kg¹ · d¹) 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; tolerance

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19188145-07$05.00/0

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