Limbic responsiveness to procaine in cocaine-addicted subjects

Objective: The limbic system plays a critical role in motivation, emotional expression, and memory. The authors investigated whether a state of permanent limbic neuronal hyperexcitability, or sensitization, is present in cocaine addicts as a consequence of repeated cocaine use. Method: Single photon emission computed tomography (SPECT) of regional cerebral blood flow (rCBF) was used to compare the central nervous system response to the limbic stimulus procaine in 10 cocaine-dependent male patients and 10 healthy comparison male subjects. Results: The cocaine-addicted subjects demonstrated bilateral activation of the orbitofrontal cortex after the procaine challenge, whereas the comparison subjects showed activation of the anterior cingulate, bilateral insular, and right amygdalar regions. After receiving placebo, the cocaine-addicted subjects showed markedly lower rCBF in the bilateral orbitofrontal cortex than the comparison subjects. Conclusions: The pattern of hypoperfusion in the placebo state followed by heightened activation with procaine in the cocaine-addicted subjects is similar to the pattern of interictal hypoperfusion and ictal hyperperfusion that has been observed in subjects with epilepsy. The findings for the cocaine-addicted subjects may thus represent evidence of localized (orbitofrontal) sensitization.