Context-controlled nicotine-induced changes in the labeling of serotonin (5-HT)2A and 5-HT2C receptors in the rat...

We have previously demonstrated that serotonin (5-HT)2A and 5-HT2C receptor ligands modulate the sensitizing effects of nicotine. In the present study we used male rats to verify the hypothesis that the binding pattern of 5-HT2A and 5-HT2C receptors in the brain is altered by chronic nicotine treatment in different environments.

Rats were given repeatedly vehicle or nicotine in different sensitizing regimens (home or experimental cages). On day 10, animals were challenged with nicotine (expression of nicotine sensitization) or vehicle in either home or experimental cages, and were sacrificed immediately after the experiment.

Repeated treatment with nicotine in home cages evoked significant increases in [(3)H]ketanserin binding to 5-HT2A receptors in the prefrontal cortex, striatal subregions and ventral tegmental area as well as reductions in [(3)H]mesulergine binding to 5-HT2C receptors in subregions of the prefrontal cortex. In contrast, nicotine paired with environmental context produced robust increases in 5-HT2A receptor labeling in the infralimbic cortex and decreased [(3)H]ketanserin binding in striatal subregions and ventral tegmental area; 5-HT2C receptor labeling in the prefrontal cortex fell.

The present data indicate that chronic nicotine administration in home cages induces bi-directional neuroplastic changes within 5-HT2A and 5-HT2C receptors in the prefrontal cortex. Pairing the nicotine with environmental context potentiates the neuroplastic response in the latter region and evokes opposite changes in 5-HT2A receptor binding in striatal and tegmental regions compared with nicotine administered in the absence of the context, indicating a modulatory role of environmental context in the expression of nicotine-induced sensitization.