Up‐regulation of β2 and α7 subunit containing nicotinic acetylcholine receptors in mouse striatum at cellular level

Abstract

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.

Cholinergic Modulation of Appetite-Related Synapses in Mouse Lateral Hypothalamic Slice

“…Overall, 43% of the neurons that were electrophysiologically characterized and relocalized after immunocytochemical analysis were MCH positive, with the majority (76%) of these MCH-positive neurons conforming to type 1 characteristics. We find a similar fraction of PF LH neurons to be MCH positive by single-cell PCR analysis (Pakkanen et al, 2005). Previous reports from other laboratories have associated the bipolar morphology and tonic firing rate profile as seen in our type 3 neurons with orexin-expressing cells in LH slices (Li et al, 2002;Eggermann et al, 2003;Gao et al, 2003).…”

“…Despite numerous studies of regulation of the expression and/or function of nAChRs by chronic nicotine exposure in vivo and in vitro (Yates et al, 1995;Olale et al, 1997;Peng et al, 1997;Ke et al, 1998;Molinari et al, 1998;Wang et al, 1998;Fenster et al, 1999;Buisson and Bertrand, 2001;Gentry and Lukas, 2002;Slotkin et al, 2002;Pakkanen et al, 2005), little information is available about the effect of prenatal nicotine exposure on synaptic activity in the CNS in general and in the hypothalamus in particular. Hence, we sought to define whether prenatal exposure to nicotine alters the inhibitory input to LH or alters cholinergic modulation in the postnatal animal.…”

Nicotine Improves Cognitive Deficits of Dopamine Transporter Knockout Mice without Long-Term Tolerance

“…Finally, such a treatment induced opposite variations of a7 nAChRs, which decreased in WT and increased in DAT KO mice. The decreased a7 nAChR density induced by chronic nicotine treatment of WT mice contrasted with previous results showing upregulation (Sparks and Pauly, 1999;Nuutinen et al, 2005;Pakkanen et al, 2005). However, in our study the administered dose of nicotine was much lower compared with other studies in mice (70 mg/ml vs increasing doses from 50 to 500 mg/ml at the end of treatment).…”

Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions

“…26 Upregulation of a7-subunit containing nAChRs after chronic nicotine treatment has been reported in several brain regions of the mouse, including striatum, midbrain and cortex. 180,181 Upregulation of human a7-subunits was shown in human embryonic kidney (HEK) cells after chronic exposure to nicotine and other receptor ligands. 182 Data on a6* receptors upregulation is less clear.…”

“…9 *Nicotine receptor upregulation, after chronic nicotine admission. 180,181 a5-containing receptor *a4b2a5N398/a4b2a5D398 Variants (refers to rs16969968) alters response to nicotine agonist. 88 *Assembly of a5 to a4b2-containing receptor, prevents receptor upregulation.…”