Addiction circuitry in the human brain

Abstract

A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.

Figure 1

Pharmacokinetics of cocaine and methamphetamine in the human brain and relationship to the drug-induced “high.” (a) Axial brain images of the distribution of [¹¹C]cocaine and [¹¹C]methamphetamine at different times (minutes) after their administration. (b) Time activity curves for the concentration of [¹¹C]cocaine and [¹¹C]methamphetamine in striatum alongside the temporal course for the “high” experienced after intravenous administration of these drugs. Modified from References and . Note that the fast brain uptake of these drugs corresponds with the temporal course of the “high,” which suggests that the “high” is associated with the “rate of dopamine increases.”

Figure 2

Dopamine (DA) changes induced by intravenous methylphenidate (MPH) in controls and in active cocaine abusers and by cocaine cues in active cocaine abusers. (a) Average nondisplaceable binding potential (BP_ND) images of [¹¹C]raclopride in active cocaine-addicted subjects and controls tested after placebo and after intravenous MPH. MPH reduced D2R availability in controls but not in cocaine-addicted subjects. Note that cocaine abusers show both decreases in baseline striatal D2R availability (placebo measure) and decreases in DA release when given intravenous MPH (measured as decreases in D2R availability from baseline). (b) Average BP_ND images of [¹¹C]raclopride in cocaine abusers tested while viewing a neutral video (nature scenes) and while viewing a cocaine-cues video (subjects administering cocaine). The cocaine cues decreased D2R in caudate and putamen. Modified from Reference . Note that cocaine-addicted subjects did not respond to intravenous MPH but instead responded to the cocaine-cues exposure.

Figure 3

Brain dopamine D2 receptors (D2R) in controls and in methamphetamine abusers and alcoholics and association between D2R in the striatum and metabolism in the orbitofrontal cortex. (a) Average brain images for D2R availability (BP_ND) in control subjects and in methamphetamine abusers obtained with [¹¹C]raclopride. (b) Average brain images for D2R availability (BP_ND) in control subjects and in alcoholics obtained with [¹¹C]raclopride. (c) Correlations between striatal D2R and metabolism in the orbitofrontal cortex (OFC) in methamphetamine abusers (top) and in alcoholics (bottom). Modified from Reference .

Figure 4

(a) Areas of the brain where metabolism differed when cocaine abusers were exposed to the cocaine-cues video with a directive to purposefully inhibit craving versus when they were exposed to the cocaine-cues video with no inhibition. Metabolism was significantly lower in the right NAc and in the right orbitofrontal cortex with inhibition than it was without inhibition (statistical parametric mapping results p < 0.005 not corrected, cluster > 100 voxels). (b) Regression slope for the differences in metabolism (inhibition versus no inhibition) in the right NAc and in the right BA 44 (r = −0.55, p < 0.006).