T. Seppa et L. Ahtee, Comparison of the effects of epibatidine and nicotine on the output of dopamine in the dorsal and ventral striatum of freely-moving rats, N-S ARCH PH, 362(4-5), 2000, pp. 444-447
The effects of the nicotinic acetylcholine receptor (nAChR) agonist epibati
dine on the extracellular concentrations of dopamine (DA) and its metabolit
es 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in th
e dorsal (caudate-putamen) and the ventral striatum (nucleus accumbens) of
freely-moving male Wistar rats were studied by in vivo microdialysis. In th
e dorsal striatum, epibatidine (3.0 mug/kg s.c.) significantly elevated the
extracellular concentrations of DA, DOPAC and HVA. In contrast, epibatidin
e did not alter the extracellular DA concentration in the ventral striatum,
but elevated significantly the concentration of DOPAC and also tended to e
levate that of HVA. In parallel experiments, nicotine (0.5 mg/kg s.c.) sign
ificantly increased DA output in the ventral striatum whereas only a modest
and non-significant increase of extracellular DA concentration was found i
n the dorsal striatum. Earlier studies have shown that the doses of epibati
dine and nicotine used in the present study are about equieffective at leas
t with respect to the analgesia-producing or hypothermic effects of the dru
gs. Comparison of the effects of epibatidine and nicotine suggests that the
responses of the mesolimbic and nigrostriatal dopaminergic systems to the
two nicotinic receptor agonists differ. Epibatidine, in contrast to nicotin
e, preferentially stimulates the nigrostriatal vs. the mesolimbic dopaminer
gic system. Therefore, novel nicotinic AChR ligands structurally related to
epibatidine may have low abuse potential.