Peroxisome Proliferator-Activated Receptors-Alpha Modulate Dopamine Cell Activity Through Nicotinic Receptors

Background: Modulation of midbrain dopamine neurons by nicotinic acetylcholine receptors (nAChRs) plays an important role in behavior, cognition, motivation, and reward. Specifically, nAChRs containing beta 2 subunits (beta 2-nAChRs) switch dopamine cells from a resting to an excited state. However, how beta 2-nAChRs can be modulated and thereby how dopamine firing activity is affected remains elusive. Because changes in dopamine cell activity are reflected in the dynamics of microcircuits generating altered responses to stimuli and inputs, factors regulating their state are fundamental. Among these, endogenous ligands to the nuclear receptor-transcription factor peroxisome proliferator-activated receptors type-alpha (PPAR alpha) have been recently found to suppress nicotine-induced responses of dopamine neurons.