? This proposal will characterize the connection between noradrenergic (NE) A2 neurons of the nucleus tractus solitarius (NTS) and dopaminergic (DA) neurons of the ventral tegmental area (VTA), and determine the role of this projection in relapse to cocaine abuse. Previous studies show that reduction of impulse activity of A2-NE neurons by an alpha-2 agonist, or blockade of D1 receptors in the prefrontal cortex, attenuates reinstatement of cocaine self-administration. Our data shows a connection from the A2-NE cells to the VTA, and that stimulation of the A2 area activates VTA-DA cells. Given the role of VTA-DA neurons in reward, these neurons are a logical potential target for effects of the A2 system in promoting relapse. We hypothesize that the activation of VTA DA neurons by A2 neurons is caused by activation of alpha adrenergic receptors. A2 NE neurons projecting to the VTA will be characterized using anatomical and neurophysiological techniques. We will determine whether alpha receptors mediate the activation of VTA neurons by A2 area stimulation. Lesion of the ascending NE ventral bundle will be used to study the effect of medullary NE in stress-induced relapse using a conditioned place preference model. Additionally, the role of alpha receptors in the VTA in stress-induced reinstatement to cocaine seeking will be determined. Finally, the firing of VTA-DA and A2-NE cells will be assessed to study associations between their activities and stress-induced reinstatement of cocaine seeking. The outcome of this research will increase our understanding of NE modulation of the DA system, and the potential role of this circuit in stress-induced relapse to cocaine abuse. ? ? ? ?
|Mejías-Aponte, Carlos A; Drouin, Candice; Aston-Jones, Gary (2009) Adrenergic and noradrenergic innervation of the midbrain ventral tegmental area and retrorubral field: prominent inputs from medullary homeostatic centers. J Neurosci 29:3613-26|