The Neurobiology of Opiate Motivation

Opiates are a highly addictive class of drugs that have been reported to possess both do-pamine-dependent and dopamine-independent rewarding properties. The search for how, if at all, these distinctmechanisms ofmotivation are related is of great interest in drug addiction research. Recent electrophysiological, molecular, and behavioral work has greatly improved our understanding of this process. In particular, the signaling properties of GABAA receptors located on GABA neurons in the ventral tegmental area (VTA) appear to be crucial to under-standing the interplay between dopamine-dependent and dopamine-independent mecha-nisms of opiate motivation. Opioid drugs play an integral part in humansociety, in part because of their well-doc-umented analgesic properties (Kanjhan 1995; Rosenblum et al. 2008). However, many of these compounds—for example, heroin and other opiates—are among the most addictive drugs in human history (Kalant 1997; Gruber et al. 2007). For these and other reasons, the elucida-tion of their motivational mechanisms of action has remained a priority for many researchers. The study of opioids and their addictive prop-erties, and the anatomical and biological mech-anisms that underlie them, has produced a slew of data implicating various receptor subtypes and neurotransmitters. In this article, we focus on research implicating the ventral tegmental area (VTA) as a crucial locus in opiate addic-tion. More specifically, we review research sug-gesting that the biology of this brain region appears crucial for the selection of either do-pamine-dependent or dopamine-independent pathways of opiate motivation