Compulsive drug use and brain reward systems

Compulsive drug intake is a hallmark of addiction, yet the neurobiological mechanisms that contribute to the loss of control over drug consumption remain unclear. A better understanding of the mechanisms that drive compulsive drug taking may reveal targets for the development of novel therapeutics to alleviate this maladaptive behavioral state. Drug use is initiated primarily to obtain the stimulatory effects of addictive drugs on brain reward systems, an action that can be measured as drug-induced lowering of intracranial self - stimulation (ICSS) thresholds in rats and mice. Paradoxically, excessive drug intake can result in decreased activity of reward systems, reflected in elevated ICSS. Such drug-induced deficits in brain reward function likely reflect the engagement of compensatory mechanisms to counter drug effects. Recent evidence suggests that compulsive drug intake may develop in response to such adaptive decreases in brain reward systems. Further, environmental stimuli repeated paired with the actions of addictive drugs can attain hedonic salience to negatively regulate brain reward systems, and may thereby serve as a novel source of drug craving. The aim of this chapter is to review the impact of excessive drug consumption and drug-paired environmental stimuli on brain reward function, discuss the role for reward pathways in driving compulsive drug taking, and present potential neurobiological mechanisms that may underlie these processes.