Modulation of dopamine release by the nicotinic agonist epibatidine in the frontal cortex and the nucleus accumbens of naive and chronic nicotine treated rats.
The effect of the nicotinic acetylcholine receptors (nAChRs) agonist (+/-)epibatidine on the modulation of dopamine (DA) release was investigated by microdialysis in vivo in the frontal cortex and the nucleus accumbens of naive and chronic nicotine-treated awake rats. (+/-)Epibatidine (2.5 microg/kg, s.c.), contrary to (-)nicotine (0.5 mg/kg, s.c.), decreased the extracellular concentrations of DA in the brain of naive rats. Subchronic nicotine treatment (0.45 mg/kg, s.c., twice daily for 7 days) attenuated the (+/-)epibatidine induced decrease in the DA level. The extracellular concentrations of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were elevated by (+/-)epibatidine administration in both naïve and subchronic treated rats. The findings suggest that the decrease in DA extracellular concentrations induced by the high affinity nAChRs agonist (+/-)epibatidine might be due to inactivation of nAChRs, which can be overcome by subchronic treatment with nicotine. Different mechanisms in modulation of DA release appears to be involved in the rat brain by (+/-)epibatidine compare to (-)nicotine.
Bednar
Ivan
I
Department of Neurotec, Division of Molecular Neuropharmacology, Karolinska Institutet, Karolinska University Hospital, Stockholm, SE 14186 Stockholm, Sweden. ivan.bednar@neurotec.ki.se
Friberg
Linda
L
Nordberg
Agneta
A
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D011725:Pyridines; D009538:Nicotine; C082748:epibatidine; D004298:Dopamine