Fatty acid ethanolamides pinpoint nicotinic receptors and modulate neuronal excitability through nuclear receptor PPAR?

SPECIFIC AIMS OF THE STUDY 1) To investigate whether FAEs can suppress nicotine-induced stimulation of VTA dopamine (DA) neuron firing rate through the peroxisome-proliferator-activated receptor-? (PPAR?) and to elucidate their mechanism of action in an in vitro brain slice preparation. 2) To determine whether there is an interaction between PPAR? and nAChRs in VTA DA cells: particularly, to characterize the postsynaptic effects of PPAR? modulation on VTA DA neurons, and to examine the contribution of nAChRs in the effects. 3) To study whether PPAR? modulation of nAChRs in VTA DA neurons might confer DA cells to access distinct firing patterns and/or to change their firing frequency both in vivo and in vitro. 4) To examine the physiological relevance of PPAR? modulation of nAChR stimulation through behavioral analysis.