A single (-)-nicotine injection causes change with a time delay in the affinity of striatal D2 receptors for antagonist, but not for agonist, nor in the D2 receptor mRNA levels in the rat substantia nigra.
The in vitro and in vivo effects of (-)-nicotine on dopamine D2 receptors in the rat neostriatum have been studied using biochemical binding, in situ hybridization and immunocytochemistry. A single i.p. injection (1 mg/kg) of (-)-nicotine resulted in a reduction of the KD value of the D2 antagonist [3H]raclopride binding sites in rat neostriatal membrane preparations at 12 h without any significant change in the Bmax value. This action of (-)-nicotine was counteracted by pretreatment 15 min earlier with the nicotine antagonist mecamylamine (1 mg/kg, i.p.). However, the KD and the Bmax values of the D2 agonist [3H]NPA binding sites in the rat neostriatal membrane preparations were not significantly affected 0.5-48 h after a single i.p. injection with 1 mg/kg of (-)-nicotine. No significant change in neostriatal D2 receptor mRNA levels was observed at any time interval after the (-)-nicotine injection. No significant change was observed in tyrosine hydroxylase (TH) immunoreactivity in either the substantia nigra or the neostriatum, nor in nigral TH mRNA levels during the time interval studied (4-24 h posttreatment). Furthermore, addition of low (10 nM) or high (1 microM) concentrations of (-)-nicotine in vitro to rat neostriatal membranes did not alter the characteristics of [3H]raclopride or [3H]NPA binding. These results indicate that a single (-)-nicotine injection can produce a selective and delayed increase in the affinity of D2 receptors for the antagonist, but not for the agonist without modifying the levels of D2 receptor mRNA, probably via the activation of central nicotinic receptors.
Li
X M
XM
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Zoli
M
M
Finnman
U B
UB
Le Novère
N
N
Changeux
J P
JP
Fuxe
K
K
D000818:Animals; D001483:Base Sequence; D018491:Dopamine Agonists / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007274:Injections, Intraperitoneal; D008297:Male; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase