Psychiatric Pathophysiology: Addiction

Psychiatric Pathophysiology: Addiction

Addiction is a complex maladaptive behavior produced by re-peated exposure to rewarding stimuli (O’Brien, 2001). There are two primary features common to both natural and pharmacologi-cal stimuli that elicit addiction. First, the rewarding stimulus as-sociated with the addiction is a compelling motivator of behavior at the expense of behaviors leading to the acquisition of other rewarding stimuli. Thus, individuals come to orient increasing amounts of their daily activity around the acquisition of the re-warding stimulus to which they are addicted. Secondly, there is a persistence of craving for the addictive stimulus, combined with an inability to regulate the behaviors associated with obtaining that stimulus. Thus, years after the last exposure to an addictive stimulus, re-exposure or environmental cues associated with that stimulus will elicit behavior aimed at obtaining the reward.

During the course of repeated exposure to strong motiva-tionally relevant stimuli, specific brain nuclei and circuits become engaged that mediate the addicted behavioral response. It is gener-ally thought that different rewarding stimuli involve different brain circuits, but also that there are regions of overlap forming a common substrate for all addictive stimuli. Studies using animal models of re-ward and addiction have focused on subcortical brain circuits known to be involved in drug reward, such as the dopamine projection from the ventral mesencephalon to the nucleus accumbens (Koob and LeMoal, 2001; Everitt and Wolf, 2002). Accordingly, molecular and electrophysiological studies of the cellular plasticity mediating the emergence of addictive behaviors have focused on the nucleus ac-cumbens and ventral mesencephalon. However, over the last decade studies have emerged from both the animal literature and neuroim-aging of drug addicts indicating that the expression of addicted be-haviors such as sensitization and craving involves regions of the cor-tex and allocortex (Pierce and Kalivas, 1997; Volkow and Fowler, 2000; Grant et al., 1996; Childress et al., 1999). In this regard, two regions have come to be most closely associated with craving, the amygdala and frontal cortex (including the anterior cingulate and ventral orbitofrontal cortex). Prior to describing circuitry underly-ing the state of addiction, we will briefly examine the neurobiology associated with the development of the addicted state.