The α4β2 nicotine acetylcholine receptor agonist ispronicline induces c-Fos expression in selective regions of the rat forebrain

The dominant nicotine acetylcholine receptor (nAChR) subtype in the brain is the pentameric receptor containing both α4 and β2 subunits (α4β2). Due to the lack of selective agonists it has not been ruled out what neuronal circuits that are stimulated after systemic administration with nicotine. We used the novel and selective α4β2 receptor agonist ispronicline (10 and 30 mg/kg s.c.) to localise the activated neurons in the rat forebrain using c-Fos-immunoreactivity as a marker of immediate neuronal activity. In the hypothalamic paraventricular nucleus, a large increase of c-Fos-positive cells was found only within its medial part. In addition, an increased number of c-Fos-immunoreactive cells were observed in the central nucleus of the amygdala, and the dorsolateral part of the bed nucleus of the stria terminalis. The restricted distribution of c-Fos to these areas, all of which are directly or indirectly involved in acute stress regulation after a single dose of ispronicline, supports earlier studies that the α4β2 receptors are strongly involved in nicotine-dependent activation of the hypothalamo-pituitary adrenocortical axis.

► Ispronicline produces an increase in c-Fos in only a few restricted areas.
► These areas overlap only partly with those earlier reported for nicotine.
► Emphasis of the role of the α4β2 nAChR in these effects.
► Dose-dependent induction in the hypothalamic PVN and the Ce of the amygdala.