Chronic nicotine treatment counteracts dopamine D2 receptor upregulation induced by a partial meso-diencephalic hemitransection in the rat.
To further elucidate the previously demonstrated protective actions of nicotine on lesioned nigrostriatal dopamine (DA) systems (Janson and Møller, Neuroscience, 57 (1993) 931-941), the present receptor binding experiments were carried out. Rats were partially hemitransected at the meso-diencephalic junction and the effects of chronic continuous (-)nicotine treatment (osmotic pumps s.c., 0.125 mg/kg/h, 14 days) on [3H]N-propylnorapomorphine ([3H]NPA) and [3H]methylcarbamylcholine ([3H]MCC) binding were investigated in striatal coronal sections to study the agonist binding sites of DA D2 receptors and nicotinic cholinoceptors, respectively. In saline-treated but not in nicotine-treated rats, the lesion led to an increased Bmax value of [3H]NPA binding. The Bmax value of [3H]MCC binding was increased by nicotine treatment and decreased by the partial hemitransection. These results indicate that chronic nicotine treatment counteracts the lesion-induced upregulation of the high-affinity agonist binding site of the DA D2 receptor, which may be explained by an increased presence of DA via a protective effect of nicotine on neostriatal DA terminals. This action of nicotine may be of interest in the treatment of neurodegenerative diseases such as Parkinson's disease.
Janson
A M
AM
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Hedlund
P B
PB
Fuxe
K
K
von Euler
G
G
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D001345:Autoradiography; D002217:Carbachol / Q000031:analogs & derivatives / Q000378:metabolism; D004027:Diencephalon / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D008024:Ligands; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
D018491:Dopamine Agonists; D008024:Ligands; D017448:Receptors, Dopamine D2; D011978:Receptors, Nicotinic; C053765:N-methylcarbamylcholine; C009074:N-n-propylnorapomorphine; D009538:Nicotine; D002217:Carbachol; D001058:Apomorphine