| First Author | Metaxas A | Year | 2013 |
| Journal | Neuropharmacology | Volume | 71 |
| Pages | 228-36 | PubMed ID | 23583933 |
| Mgi Jnum | J:328391 | Mgi Id | MGI:6870753 |
| Doi | 10.1016/j.neuropharm.2013.03.023 | Citation | Metaxas A, et al. (2013) Genetic deletion of the adenosine A(2A) receptor prevents nicotine-induced upregulation of alpha7, but not alpha4beta2* nicotinic acetylcholine receptor binding in the brain. Neuropharmacology 71:228-36 |
| abstractText | Considerable evidence indicates that adenosine A(2A) receptors (A(2A)Rs) modulate cholinergic neurotransmission, nicotinic acetylcholine receptor (nAChR) function, and nicotine-induced behavioural effects. To explore the interaction between A(2A) and nAChRs, we examined if the complete genetic deletion of adenosine A(2A)Rs in mice induces compensatory alterations in the binding of different nAChR subtypes, and whether the long-term effects of nicotine on nAChR regulation are altered in the absence of the A(2A)R gene. Quantitative autoradiography was used to measure cytisine-sensitive [(1)(2)(5)I]epibatidine and [(1)(2)(5)I]alpha-bungarotoxin binding to alpha4beta2* and alpha7 nAChRs, respectively, in brain sections of drug-naive (n = 6) or nicotine treated (n = 5-7), wild-type and adenosine A(2A)R knockout mice. Saline or nicotine (7.8 mg/kg/day; free-base weight) were administered to male CD1 mice via subcutaneous osmotic minipumps for a period of 14 days. Blood plasma levels of nicotine and cotinine were measured at the end of treatment. There were no compensatory developmental alterations in nAChR subtype distribution or density in drug-naive A(2A)R knockout mice. In nicotine treated wild-type mice, both alpha4beta2* and alpha7 nAChR binding sites were increased compared with saline treated controls. The genetic ablation of adenosine A(2A)Rs prevented nicotine-induced upregulation of alpha7 nAChRs, without affecting alpha4beta2* receptor upregulation. This selective effect was observed at plasma levels of nicotine that were within the range reported for smokers (10-50 ng ml(-)(1)). Our data highlight the involvement of adenosine A(2A)Rs in the mechanisms of nicotine-induced alpha7 nAChR upregulation, and identify A(2A)Rs as novel pharmacological targets for modulating the long-term effects of nicotine on alpha7 receptors. |
