A class of medications currently being developed by several pharmaceutical companies may help drug abuse patients avoid relapse after experiencing stress. Called CRF antagonists, the compounds block the action of corticotropin-releasing factor (CRF), a naturally occurring chemical in the brain. Scientists think that CRF may play a key role in producing arousal, anxiety, and other emotional responses to stress.
Dr. Yavin Shaham, formerly of the University of Toronto and now in NIDA's Intramural Research Program in Baltimore; NIDA grantee Dr. Jane Stewart of Concordia University in Montreal; and their colleagues at Concordia University and the Addiction Research Foundation in Toronto have conducted a series of studies to determine whether CRF antagonists can prevent stress-induced relapse to drug-seeking in rats. In these studies, rats were trained to press a lever to receive a dose of cocaine or heroin. After the rats learned this behavior, the supply of drugs was terminated so that pressing the lever no longer resulted in a dose of drug. As a result, the rats reduced their lever pressing to practically nothing. However, when the rats were given mild intermittent footshocks for 10 to 15 minutes, they started to press the lever again as soon as it became available, even though they did not receive any drug. This indicates that stress can reinstate drug seeking in rats, just as it is reported to do in human addicts, says Dr. Stewart.
The researchers found that giving the rats a CRF antagonist prior to giving them footshocks could greatly reduce the rate at which the rats would press the lever again. However, the compound had no effect when the rats were pressing a lever to receive a drop of sugar solution that they could drink. "This suggests that the CRF antagonist blocks stress-induced relapse to drug seeking specifically and does not produce its effects by interfering with the animal's ability to press the lever," says Dr. Stewart.
Results such as these have interested staff in NIDA's Medications Development Division (MDD) in the potential of CRF antagonists for treating drug abuse relapse. "What's so interesting about CRF antagonists is that evidence suggests that they may be useful in treating relapse to a variety of drugs, including cocaine, heroin, and nicotine," says Dr. Jane Acri of MDD. "This is particularly important considering that people who abuse drugs often abuse a number of different drugs."
Shaham, Y.; Erb, S.; Leung, S.; Buczek, Y.; and Stewart, J. CP-154,526, a selective, non-peptide antagonist of the corticotropin-releasing factor1 receptor attenuates stress-induced relapse to drug seeking in cocaine- and heroin-trained rats. Psychopharmacology 137:184-190, 1998.