Nicotine metabolism in cigarette smokers and nonsmokers

Kyerematen, Gabriel A.; Morgan, Monica L; Chattopadhyay, Balaka; deBethizy, J D; Vesell, Elliot S.

doi:10.1038/clpt.1994.14

Cited by 4 publications

(1 citation statement)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the tobacco alkaloid and active nicotine metabolite nornicotine serves as a both a psychostimulant and positive reinforcer in rats (Bardo et al, 1999; Green et al, 2001). Nornicotine has an 8X longer plasma half-life compared to nicotine in both human smokers and non-smokers (Kyerematen et al, 1994), and is known to accumulate in rat brain with repeated intermittent peripheral injections (Ghosheh et al, 1999). Thus, even the short-access schedule used here would be expected to provide an extended post-session period of nicotinic receptor activation, which is a critical component for the addictive process.…”

Section: Discussionmentioning

confidence: 99%

Nicotine self‐administration remodels perineuronal nets in ventral tegmental area and orbitofrontal cortex in adult male rats

Vázquez-Sanromán

Monje²,

Bardo

2016

Addiction Biology

View full text Add to dashboard Cite

Nicotine, a major psychoactive component of tobacco smoke, alters GABA modulation of dopamine (DA) neurons in the ventral tegmental area (VTA). Changes in structural neuroplasticity can occur in GABAergic parvalbumin (PRV) positive neurons, which are enveloped by structures of the extracellular matrix called perineuronal nets (PNNs). In the current study, rats were trained to self-administer IV nicotine (0.03 mg/kg/infusion) for 21 days in 1-h daily sessions with an incrementing fixed ratio requirement; a control group received saline infusions. At either 45 min or 72 hr after the last session, immunofluorescence measurements for PNNs, PRV and c-Fos were conducted. In VTA, nicotine self-administration reduced the number of PRV+ cells surrounded by PNNs at 45 min, as well as reducing the intensity of PNNs, suggesting a remodeling of GABA interneurons in this region; the number of PRV+ cells surrounded by PNNs was also reduced at 72 hr. A similar reduction of PNNs occurred in orbitofrontal cortex (OFC), but not in medial prefrontal cortex (PrL or IL), 45 min after the last session; PNNs were not detected in nucleus accumbens (shell or core). The reduction of PNNs in VTA and OFC was unrelated to c-Fos+ cells, as the percent of WFA+ cells co-expressing c-Fos was decreased in OFC, but not in VTA. Thus, nicotine self-administration remodeled PNNs surrounding GABA interneurons in VTA and its indirect connections to OFC, suggesting a new possible molecular target where nicotine-induced neuroplasticity takes place. PNN manipulations may prevent or reverse the different stages of tobacco addiction.

show abstract

Section: Discussionmentioning

confidence: 99%