Abstract

Stress is the non-specific response to adjust the balance of body function following danger, challenge, continuous stimulus. The immobilization stress using plastic rodent restrainer among the several stressor used to animal model to investigat the biological effects of psychological stress. Drugs of abuse cause long-lasting changes in brain that underlie the behavioral abnormalities associated with drug addiction. What is not understood is why, when drugs are unavailable for long periods or even when users succeed in curbing their own drug use for extended periods, users remain vulnerable to relapse. Relapse is a major characteristic of drug addiction, and remain the primary problem for the treatment of drug abuse. The foodshock stressor reliably reinstated extinguished cocaine- and heroine-taking behavior. Rats trained to self-administer cocaine, exposure to acute intermittent footshock stress induces reinstatement of cocaine-taking behavior after prolonged extinction sessions and after a 4-to 6-week drug-free period. Several findings suggest that glucocorticoid hormones are involved in determining the propensity of an individual to develop cocaine abuse. The selective inactivation of the glucocorticoid (GR) receptor gene in the brains of mice profoundly flattened the dose-response function for cocaine intravenous self-administration and suppressed sensitization. Recent interest has focused on the role of amygdala in the learned association that occur during the process of drug addiction and relapse. The basolateral amygdala (BLA) complex plays a critical role in this behavior, because permanent lesions or reversible pharmacological inactivation of the BLA attenuates conditioned-cued reinstatement without affecting cocaine self-administration or cocaine-primed reinstatement. Pretreatment with the selective CRF1 receptor antagonist, CP-154,526, significantly attenuated the reinstatement effect of the stressor in both heroin- and cocaine-trained rats. Collectively, It has been known that several specific brain regions which is closely related with stress-induced activation have important roles in the drug abuse (relapse), and specific CRF receptor, glutamate receptor and glucocorticoid receptor antagonists suppressed the self-administration of drug. These results suggest a clue to develop the anti- narcotic drugs and provide new therapeutic strategies to treat drug addiction. (Korean J Str Res 2005;13:65∼72)

• Keywords: Immobilization, Amygdala, Drug abuse, Cocaine, CRF, Glucocorticoid