Acute Effects of Cocaine on Human Brain Activity and Emotion

Abstract

We investigated brain circuitry mediating cocaine-induced euphoria and craving using functional MRI (fMRI). During double-blind cocaine (0.6 mg/kg) and saline infusions in cocaine-dependent subjects, the entire brain was imaged for 5 min before and 13 min after infusion while subjects rated scales for rush, high, low, and craving. Cocaine induced focal signal increases in nucleus accumbens/subcallosal cortex (NAc/SCC), caudate, putamen, basal forebrain, thalamus, insula, hippocampus, parahippocampal gyrus, cingulate, lateral prefrontal and temporal cortices, parietal cortex, striate/extrastriate cortices, ventral tegmentum, and pons and produced signal decreases in amygdala, temporal pole, and medial frontal cortex. Saline produced few positive or negative activations, which were localized to lateral prefrontal cortex and temporo-occipital cortex. Subjects who underwent repeat studies showed good replication of the regional fMRI activation pattern following cocaine and saline infusions, with activations on saline retest that might reflect expectancy. Brain regions that exhibited early and short duration signal maxima showed a higher correlation with rush ratings. These included the ventral tegmentum, pons, basal forebrain, caudate, cingulate, and most regions of lateral prefrontal cortex. In contrast, regions that demonstrated early but sustained signal maxima were more correlated with craving than with rush ratings; such regions included the NAc/SCC, right parahippocampal gyrus, and some regions of lateral prefrontal cortex. Sustained negative signal change was noted in the amygdala, which correlated with craving ratings. Our data demonstrate the ability of fMRI to map dynamic patterns of brain activation following cocaine infusion in cocaine-dependent subjects and provide evidence of dynamically changing brain networks associated with cocaine-induced euphoria and cocaine-induced craving.

Brief Social Defeat Stress: Long Lasting Effects on Cocaine Taking During a Binge and Zif268 mRNA Expression in the Amygdala and Prefrontal Cortex

“…Specifically, amphetamine weakened the suppressive effect of stress on the functional activity of cells in the CeA and MeA (see Figure 6). Interestingly, administration of cocaine in cocaine-dependent individuals reduces the functional activity of amygdaloid neurons, and this inhibition has been suggested to correlate with cocaine craving (Breiter et al, 1997). Electrophysiological studies indicate that infralimbic projection neurons synapse directly onto GABAergic intercalated cells in the CeA (Sesack et al, 1989;Royer et al, 1999;Quirk et al, 2003), which may be the source of amphetamine-induced decreases in functional activation in the CeA as observed herein.…”

An fMRI Study of the Effect of Amphetamine on Brain Activity,

“…One way to use fMRI to measure the effects of amphetamine on the baseline levels of neural activity, independent of task, might be to administer the drug intravenously. Indeed, it has been reported that intravenous infusions of cocaine, another psychostimulant, induced regionally specific fMRI activation (Breiter et al 1997) that was consistent with known neuroanatomical pathways and anatomical measurements of stimulant effects (Vollenweider et al 1998).…”

Extinction of Cocaine Self-Administration Produces a Differential Time-Related Regulation of Proenkephalin Gene Expression in Rat Brain

“…Several animal studies have suggested the "extended amygdala" as a neural substrate for the behavioral effects of self-administered cocaine (Robledo and Koob 1993;Caine and Koob 1994;Hurd et al 1997;McGregor and Roberts 1993;Robbins et al 1989;Robledo et al 1996). In humans, recent evidence from brain-imaging studies suggest a role for dopamine-rich brain regions, including the nucleus accumbens and amygdala, in cocaine craving (Grant et al 1996;Breiter et al 1997;Childress et al 1999). Along this line, considering the particular conditions of this work, it is tempting to speculate that, in addition to previously documented inhibition of mesocorticolimbic activity (Rossetti et al 1992;Kuhar and Pilotte 1996), a decrease in proenkephalin gene expression in the Ce may represent a possible mechanism mediating in cocaine withdrawal states.…”