Addiction is a tremendous health and financial burden on our society. A large literature indicates that dopaminergic transmission in the brain plays a key role in the reward system that mediates many behavioral responses to drugs of abuse. The ventral tegmental area (VTA) is a critical dopaminergic cell nucleus that is activated by multiple drugs of abuse, and is an integral component of the reward system. In addition though, a more dispersed group of dopamine neurons rostral and caudal to the VTA exists within the periaqueductal grey (PAG) referred to as the A10dc group of neurons. Little is known of the function of these neurons;however, recent studies have indicated that these cells play important roles in pain processing and in reward sensation. Moreover, these dopaminergic neurons have a discrete projection into the forebrain, predominantly into a region of the brain referred to as the extended amygdala. A large literature indicates that 1) the extended amygdala plays an important role in long-term modifications of behavior produced by drugs of abuse, and 2) dopaminergic transmission in the extended amygdala is key to some reward and anxiety responses. The advent of new genetic reporter strategies has allowed for the generation of new mouse reagents that allow investigators to target neurons for study that heretofore could not be isolated for examination. We propose to characterize and utilize two lines of mice already in our mouse colony that express enhanced green fluourescent protein under the direction of either the tyrosine hydroxylase promotor, or as a fusion construct with the endogenous dopamine transporter, to allow the a priori identification of A10dc neurons for electrophysiological analysis. Addiction poses an enormous health and financial burden on our society. Currently, our understanding of the brain circuitries involved in addiction is far from complete. The successful completion of these proposed studies will result in important new information about neurons that may be involved in addiction, potentially creating new targets for therapeutics development.
Addiction poses an enormous health and financial burden on our society. Currently, our understanding of the brain circuitries involved in addiction is far from complete. The successful completion of these proposed studies will result in important new information about neurons that may be involved in addiction, potentially creating new targets for therapeutics development.
| Williams, Megan A; Li, Chia; Kash, Thomas L et al. (2014) Excitatory drive onto dopaminergic neurons in the rostral linear nucleus is enhanced by norepinephrine in an ?1 adrenergic receptor-dependent manner. Neuropharmacology 86:116-24 |
