Expectation Modulates Human Brain Responses to Acute Cocaine: A Functional Magnetic Resonance Imaging Study

Background Human expectation of psychoactive drugs significantly alters drug effects and behavioral responses. However, their neurophysiological mechanisms are not clear. This study investigates how cocaine expectation modulates human brain responses to acute cocaine administration. Methods Twenty-six right-handed non–treatment-seeking regular cocaine abusers participated in this study. Changes in blood oxygenation level-dependent (BOLD) signals were measured, and online behavioral ratings during cocaine expectation and acute cocaine administration were recorded. Results Distinct regional characteristics in BOLD responses to expected and unexpected cocaine infusions were observed in the medial orbitofrontal gyrus (Brodmann area [BA] 11), frontal pole (BA 10), and anterior cingulate gyrus regions. Active engagement in the amygdala and the lateral orbitofrontal cortex (OFC; BA 47) by unexpected but not expected cocaine infusion was discovered. Cocaine expectation did not change BOLD responses to acute cocaine administration in a set of subcortical substrates, the nucleus accumbens, ventral putamen, ventral tegmental area, and thalamus. Conclusions These results suggest that cocaine expectation modulates neural-sensitivity adaptation between the expected events and the actual outcomes but did not modulate the pharmacological characteristics of cocaine. In addition, the amygdala–lateral OFC circuitry plays an important role in mediating stimulus-outcome relations and contextual factors of drug abuse.