Effect of Nicotine on the Turnover Rate of Catecholamine in the Rat Brain

Abstract

Acute effects of in vivo nicotine application on turnover rates of dopamine (DA), norepinephrine (NE), and epinephrine (EP) in the rat brain regions were examined. Turnover rates of the amines were evaluated by measuring tissue content of a metabolite of DA and NE, dihydroxyphenylacetic acid and 3-methoxy-4-hydroxyphenylethylene glycol, respectively, and/or by comparing decline of contents of the amines after blockade of synthesis. Synthesis was blocked by α-methyl-p-tyrosine 300 mg/kg, i.p., and fusaric acid 80 mg/kg, i.p., an inhibitor of tyrosine hydroxylase and dopamine-β-hydroxylase, respectively. Three kinds of the amines and the metabolites were measured using HPLC-ECD methods. Injection of nicotine (0.4–1.0 mg/kg, s.c.) increased DA turnover rate in hypothalamus, thalamus, and pons/medulla, and NE turnover rate in striatum, hypothalamus, thalamus, midbrain, pons/medulla, and cerebellum. As a parameter of turnover rate, nicotine-induced increases in content of the metabolites were more sensitively detected than nicotine-induced decreases in DA and NE content itself after blockade of synthesis. These facilitatory effects of nicotine on turnover rate of DA and NE were antagonized by pretreatment with mecamylamine 5 mg/kg, i.p., a centrally acting nicotinic antagonist, but not by hexamethonium 10 mg/kg, i.p., an antagonist poorly penetrating into the brain. Nicotine also tended to accelerate the disappearance of EP content caused by fusaric acid in hypothalamus, thalamus, midbrain, and pons/medulla. These findings demonstrate that nicotine increases the turnover rate of catecholaminergic neurons in various regions via direct activation of central nicotinic receptors.KeywordsTyrosine HydroxylaseTurnover RateFusaric AcidCatecholaminergic NeuronTeratogenic RiskThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.