c‐Fos marking of identified midbrain neurons coactive after nicotine administration in‐vivo

Abstract

Despite the reduced life expectancy and staggering financial burden of medical treatment associated with tobacco smoking, the molecular, cellular, and ensemble adaptations associated with chronic nicotine consumption remain poorly understood. Complex circuitry interconnecting dopaminergic and cholinergic regions of the midbrain and mesopontine tegmentum are critical for nicotine associated reward. Yet our knowledge of the nicotine activation of these regions is incomplete, in part due to their cell type diversity. We performed double immunohistochemistry for the immediate early gene and surrogate activity sensor, c-Fos, and markers for either cholinergic, dopaminergic or GABAergic cell types in mice treated with nicotine. Both acute (0.5 mg/kg) and chronic (0.5 mg/kg/day for 7 days) nicotine strongly activated GABAergic neurons of the interpeduncular nucleus and medial terminal nucleus of the accessory optic tract (MT). Acute but not chronic nicotine also activated small percentages of dopaminergic and other neurons in the ventral tegmental area (VTA) as well as noncholinergic neurons in the pedunculotegmental and laterodorsal tegmental nuclei (PTg/LDTg). Twenty four hours of nicotine withdrawal after chronic nicotine treatment suppressed c-Fos activation in the MT. In comparison to nicotine, a single dose of cocaine caused a similar activation in the PTg/LDTg but not the VTA where GABAergic cells were strongly activated but dopaminergic neurons were not affected. These results indicate the existence of drug of abuse specific ensembles. The loss of ensemble activation in the VTA and PTg/LDTg after chronic nicotine represents a molecular and cellular tolerance which may have implications for the mechanisms underlying nicotine dependence.

Sex differences in the impact of electronic nicotine vapor on corticotropin-releasing factor receptor 1 neurons in the mouse ventral tegmental area

“…Whereas cFos expression reflects a snapshot of neuronal activity ~30-60 minutes prior to the time of sacrifice 55 while the animals are actively being exposed to the vapor. The cFos increase following acute and decrease following chronic nicotine vapor exposure is consistent with previous studies examining the patterns of activity following systemic nicotine exposure 51 .…”

Electronic Vaporization of Nicotine Salt or Freebase produces differential effects on metabolism, neuronal activity and behavior in male and female C57BL/6J mice

“…The VTA and its dopaminergic activity is thought to underlie reward signaling in the brain and is a major target of drugs of abuse, including nicotine [ 24 ]. Nicotine has previously been shown to increase cell firing [ 25 , 26 ] and cFos expression [ 27 ] in the VTA. Additionally, studies have found that both rats [ 8 ] and mice [ 7 ] will self-administer nicotine vapor.…”

Galaninergic and hypercapnia-activated neuronal projections to the ventral respiratory column

“…Western blotting with mouse anti-tyrosine hydroxylase (TH) antibody confirmed that it specifically recognizes a 55–60 kDa protein in ventral tegmental area lysates (manufacturer's datasheet; Gumbs et al 2019 ). Sheep anti-TH antibody was previously characterised by Baur et al ( 2018 ). Western blot of rat brain corpus striatum homogenates show a single band of ∼62 kDa (manufacturer's datasheet; Haycock and Haycock 1991 ; Kansy et al 2004 ).…”