The Mesolimbic Dopaminergic Reward Circuitry

Research into impulsivity generally focuses on inhibitory failures. A new area of neurobiological research investigates the motivational component of impulsive behavior. As such, a reward system, subserved by the meso-limbic dopaminer-gic pathways, is gaining increasing attention. This reward circuitry appears to be geared towards appetitive states, i.e., eager anticipation of reward, rather than consummatory states, or the pleasure associated with obtaining the reward, which may comprise a distinct system (Panksepp, 1998). Moreover, this system appears to comprise a generalized approach to reward stimuli and is not specific to any class of reward, e.g., food, sex, or psychoactive substances (Panskepp, 1998). The initial theories of the reward circuitry derive from animal models (Panskepp, 1998; Koob, 2000; Becerra, 2001), which implicated several subcortical areas, including parts of the amygdala and the nucleus accumbens (Becerra, 2001; Koob, 2000; Panksepp, 1998). These areas are richly innervated by meso-limbic dopaminergic tracts originating in the ventral tegmental area (Becerra, 2001; Koob, 2000) and coursing through the medial forebrain bundle of the lateral hypothalamus (Panksepp, 1998).

In humans, brain imaging allows the closest analogue of in vivo animal studies. The notion of anticipatory, appetitive states is particularly suggestive of drug craving; likewise, the impetus for investigating the reward circuitry in.humans has largely come out of addiction research. There are a few imaging studies following direct infusion of cocaine or methelphenidine (Volkow et al, 1999; Becerra, 2001). Most studies utilize videotapes of drug use or drug paraphernalia as visual stimuli to induce drug craving, which was seen as a rough equivalent of reward-motivated states (Wexler et al, 2001, Volkow et al, 1999). Technical limitations often preclude sensitive imaging of small subcortical regions, but several studies have demonstrated changes in the nucleus accumbens (Becerra et al, 2001, Wexler et al, 2001, Grant et al, 1996) and the amygdala (Wexler et al, 2001, Childress et al, 1999, Grant et al, 1996) following either direct infusion of a drug of abuse or activation with cue-induced craving. A few studies have noted involvement of the caudate and other striatal areas (Garavan et al, 2000, Childress et al, 1999; Grant et al, 1996).

As would be expected in humans, there was also extensive cortical involvement. Most studies showed orbito (Volkow, 1999; Grant et al, 1996), medial (Garavan et al, 2000, Grant et al, 1996) or dorsolateral prefrontal activation (Garavan et al, 2000, Maas et al, 1998, Wexler et al, 2001, Grant et al, 1996) with cue induced craving or infusion (Volkow et al, 1999), suggesting significant cognitive elaboration of emotional/ motivational states in humans. Inferior and anterior parietal regions have also been identified (Garavan et al, 2000, Grant et al, 1996) as have temporal areas, (Garavan etal, 2000, Childress etal, 1999, Becerra etal, 2001), which may be related to memory demands. An area that has received particular attention is the anterior cingulate gyrus (Garavan et al, 2000, Maas et al, 1998, Wexler et al, 2001, Childress et al, 1999, Volkow et al, 1999). The anterior cingulate may subserve a complex array of psychological functions, with affective/motivational, cognitive and sensory components (Liotti et al, 2000, Shin et al, 2000).

There are to date, no investigations specifically into the reward circuitry in antisocial populations but we could postulate that such groups would show functional abnormalities in this system. Soderstrom et al (2001) found that elevated levels of CSF homovanillic acid (HVA), an index of dopaminergic function, predicted to high scores on the PCL-R. Furthermore, robust evidence of the high comorbidity of substance abuse and antisocial personality disorder adds support to this hypothesis (Fu et al, 2002).

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