Up-regulation of beta2 and alpha7 subunit containing nicotinic acetylcholine receptors in mouse striatum at cellular level.
Nicotine releases dopamine in the brain by activating neuronal nicotinic acetylcholine receptors (nAChRs). Chronic nicotine treatment increases the number of nAChRs, which represents plasticity of the brain. Together these phenomena have been suggested to have a role in the development of nicotine addiction. In the brain nAChRs can be localized synaptically, extrasynaptically or intracellularly. The purpose of these studies was to clarify the effects of chronic nicotine treatment on the localization of beta2 and alpha7 nAChR subunits in brain areas involved in nicotine addiction. Nicotine was administered orally in drinking water to male NMRI mice for 7 weeks. At the end of chronic nicotine treatment the localization of the nAChR subunits was studied in the dorsal striatum and in the ventral tegmental area (VTA) by using electron microscopy. In the brain areas studied beta2 and alpha7 subunits were localized presynaptically and postsynaptically in axon endings and in dendrites. In both areas the majority of the beta2 and alpha7 subunits were localized at extrasynaptic sites. In response to chronic nicotine treatment the beta2 and alpha7 nAChR subunit labelling was increased at synaptic and extrasynaptic sites as well as intracellularly. This suggests that the trafficking of nAChR subunits is increased as a result of chronic nicotine treatment and nAChRs in all parts of neurons could have functional roles in the formation of nicotine addiction.
Pakkanen
Jukka S
JS
Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FIN-00014 Finland. jukka.s.pakkanen@helsinki.fi
Jokitalo
Eija
E
Tuominen
Raimo K
RK
D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D003342:Corpus Striatum / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009538:Nicotine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000235:genetics*; D015854:Up-Regulation; D017557:Ventral Tegmental Area / Q000502:physiology / Q000648:ultrastructure; D064569:alpha7 Nicotinic Acetylcholine Receptor
D009538:Nicotine; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579166:Chrna7 protein, mouse