ACUTE PHARMACOLOGICAL BLOCKADE OF CORTICOSTERONE SECRETION REVERSES FOOD RESTRICTION-INDUCED SENSITIZATION OF THE LOCOMOTOR RESPONSE TO COCAINE

Several data indicate that a blockade of stress-induced corticosterone secretion prevents the development of the stress-induced sensitizatio n of the behavioral effects of drugs of abuse. In this report we inves tigated if an acute blockade of corticosterone secretion could reverse stress-induced sensitization once it is already established. Food res triction (90% of initial body weight) was used as stressor. Corticoste rone secretion was blocked by the corticosterone synthesis inhibitor m etyrapone (100 mg/kg). After 8 days of food restriction, animals recei ved an injection of metyrapone and 3 h later they were tested either f or the locomotor response to cocaine or for the corticosterone secreti on in response to stress (restraint, 30 min). Neither metyrapone nor f ood restriction had any effect on the locomotor response to a saline i njection. In contrast, food-restricted animals, compared to ad libitum -fed controls, showed a higher locomotor response to cocaine and highe r corticosterone levels. Treatment with metyrapone totally abolished t hese effects. Food-restricted animals, receiving a single injection of metyrapone, did not differ from ad libitum-fed controls for both loco motor response to cocaine and corticosterone secretion. Metyrapone tre atment also similarly reduced the response to cocaine and corticostero ne secretion in ad libitum-fed controls. In conclusion, this study pro vides further evidence that the enhancement in drug effects produced b y stress depends on an increase in corticosterone levels. Since stress -induced sensitization is considered one of the conditions predisposin g to drug abuse, the present results might have implications for the t reatment of addiction.