Stress and Drugs of Abuse

United States

Francis Vocci, Ph.D.

A one-day meeting, entitled "Stress and Drugs of Abuse" was held in Bethesda on April 14 to assess whether "stress" and corticotropin-releasing hormone (CRH) as a possible molecular target for an anti-drug medication represented a major factor in relapse to drug use.

The consultants described the anatomical localization of CRH and its two known receptors in the brain, and the pharmacological specificity of each of the subtypes. Although CRH is widely appreciated as the initiating factor responsible for the activation of the hypothalamo-hypophysial-adrenal axis, it subserves additional functions in other parts of the brain, such as in the locus coeruleus and the basolateral nucleus of the amygdala, and it is likely that its role in drug taking behavior goes beyond its more familiar functions.

Consultants presented data showing that although activation of the hypothalamo-hypophysial-adrenal pathway via footshock could reinstate cocaine- and heroin-taking behavior, the precipitated withdrawal of THC could also activate neurons in the amygdala in which CRH is localized. Others pointed out that they have not been able to replicate some reports in the literature that indicate that behavioral sensitization to repeated cocaine does not occur in adrenalectomized animals. The possible role of other neuropeptides such as CCK was also discussed briefly.

The consultants agreed the CRH neuropeptide system was a reasonable target for an antidrug-medication, and suggested that its effects might be mediated through the reduction of anxiety that might lead to relapse to drug use. The consultants briefly discussed benzodiazepines, which are also anxiolytics. These were dismissed as potential medications for this indication because they have produce dependence and have significant side effects, including the induction of drowsiness.