Limbic activation during cue-induced cocaine craving

Abstract

Objective: Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans.

Method: Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions.

Results: During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the non-drug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex).

Conclusions: These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.

FIGURE 1. Changes in Subjective Responses to a Cocaine-Related Video Among Detoxified Cocaine Patients and Cocaine-Naive Comparison Subjects^a

^a Scores represent the change from resting baseline for items self-rated on a 10-point (0 to 9) scale. ^b Changes differed both from the patients’ own baseline responses (all t values ≥3.70, df=12, p values ≤0.003) and from the responses of the comparison subjects (one-way ANOVA: for craving, F=17.13, df=1, 18, p=0.0006; for high, F=5.87, df=1, 18, p<0.03; for wish for rush, F=6.27, df=1, 18, p=0.02).

FIGURE 2. Changes in Relative Regional Cerebral Blood Flow (rCBF) in Limbic and Comparison Brain Regions of Detoxified Cocaine Patients and Cocaine-Naive Comparison Subjects in Response to a Cocaine-Related Video^a

^a Values represent the change in regional CBF between a non-drug-related (nature) video and a cocaine-related video. Regional CBF in the cocaine patients showed a pattern of differential limbic increases and basal ganglia decreases in response to the cocaine video; this pattern did not occur in comparison subjects without a cocaine history. For these analyses, the hippocampus included the adjacent entorhinal cortex, the orbitofrontal cortex included the rectal gyrus, and the visual cortices included both primary and association cortices. ^b There were significant changes in regional CBF in response to the cocaine video for the amygdala and the anterior cingulate both within the patient group (t=6.42, df=12, p=0.00002, and t=2.75; df=12, p<0.02, respectively) and between the patients and the comparison subjects (F=6.37, df=1, 18, p<0.02, and F=4.62, df=1, 18, p<0.05, respectively). Within the cocaine group there was also a significant change in regional CBF for the temporal pole (t=4.45, df=12, p=0.0007). ^c Within the cocaine group there were significant reductions in regional CBF in response to the cocaine video for the caudate (t=4.56, df=12, p=0.0005) and the lenticular nuclei (t=2.31, df=12, p<0.04) There was also a significant difference in caudate regional CBF between the patients and the comparison subjects (F=9.46, df=1, 18, p=0.007).

FIGURE 3. Transaxial Images Illustrating the Differential Increase in Relative Regional Cerebral Blood Flow (CBF) in the Amygdala and Anterior Cingulate of a Detoxified Cocaine Patient During a Non-Drug-Related (Nature) Video and a Cocaine-Related Video^a

^a Anatomical regions of interest were first localized on the patient's MRI (the first image in each row); region templates were subsequently superimposed on ¹⁵O PET images, yielding radioactive count files for conversion to normalized (relative) regional CBF. The middle and final images in each row show relative regional CBF as measured by PET. The range on the arbitrary color scale is from 0.0 to 2.5 times background activity; whole brain average regional CBF is 1.0 on the scale. Areas with greatest relative regional CBF are shown in red; activity in the amygdala and in the anterior cingulate differentially increased during the cocaine video.