These experiments will make an essential contribution to the field of drug addiction research by fully characterizing the synaptic changes underlying processes associated with the phenomenon of drug addiction. Both the D1 receptor and the nicotinic acetylcholine receptor have been found to be crucial in behavioral changes accompanying drug exposure, and these effects are likely due to their role as important modulators of synaptic transmission within the ventral tegmental area (VTA). Using a brain-slice preparation and whole-cell patch-clamp electrophysiology, the effects of D1 agonists and antagonists on nicotinic modulation of synaptic transmission within the VTA will be assessed, providing insight into the influence of somatodendritic dopamine release upon cholinergic inputs to the VTA. Subsequently, pretreating slices with nicotine before D1 agonist or antagonist treatment will assess the impact of nicotinic receptor activation upon D1 receptor modulation of synaptic inputs in the VTA. Further studies will explore the mechanisms that functionally link these two receptor systems, with a focus on intracellular cAMP and protein kinase A- dependent phosphorylation, and an extracellular pathway mediated by adenosine levels. ? ? ?
| Chang, Ben; Daniele, Claire A; Gallagher, Keith et al. (2011) Nicotinic excitation of serotonergic projections from dorsal raphe to the nucleus accumbens. J Neurophysiol 106:801-8 |
