Effects of combined nicotine and fluoxetine treatment on conditioned place preference and adult hippocampal neurogenesis

FAILLACE, ZWILLER, BERNABEU

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2015 p. 104 - 115

0306-4522

Adult neurogenesis occurs in mammals within the dentate gyrus, a hippocampal subarea. It isknown to be induced by antidepressant treatment and reduced in response to nicotine administration.We report here that chronic, but not acute treatment of rats with the antidepressant fluoxetine wasable to abolish the decrease in adult dentate cell proliferation produced by nicotine treatment. By using the conditioned place preference (CPP) paradigm, we also gave both drugs in a context in which their rewarding properties could be measured. Fluoxetine produced a significant but less robust CPP when compared to nicotine. A single injection of fluoxetine was found to reduce nicotine-induced CPP.Moreover, the rewarding properties of nicotine were completely abolished in response to chronicfluoxetine treatment. We also measured the expression of parameters known to be associated withneurogenesis in the dentate gyrus. Both drugs increased the expression of p75 neurotrophin receptor, which promotes proliferation and early maturation of dentate gyrus cells. Expression of nicotineinduced CPP was accompanied by an increase of phospho-CREB (cyclic AMP responsive element binding protein) and HDAC2 (histone deacetylase 2) expression in the nucleus accumbens. The data suggest that fluoxetine reward, as opposed to nicotine reward, depends on dentate gyrus neurogenesis.Since fluoxetine was able to disrupt the association between nicotine and environment, thisantidepressant may be tested as a treatment for nicotine addiction using cue exposure therapy.