Abstract
Addiction is a chronic psychiatric disease which represents a global problem, and stress can increase drug addiction and relapse. Taking into account frequent concomitance of nicotine dependence and stress, the purpose of the present study was to assess behavioral and biochemical effects of chronic unpredictable mild stress (CUMS) exposure on nicotine reward in rats measured in the conditioned place preference (CPP) paradigm. Rats were submitted to the CUMS for 3 weeks and conditioned with nicotine (0.175 mg/kg) for 2 or 3 days. Our results revealed that only CUMS-exposed animals exhibited the CPP after 2 days of conditioning indicating that stressed rats were more sensitive to the rewarding properties of nicotine and that chronic stress exacerbates nicotine preference. Administration of metyrapone (50 mg/kg), a glucocorticosteroid antagonist, and imipramine (15 mg/kg), an antidepressant, abolished nicotine CPP in stressed rats after 2 days of conditioning. The biochemical experiments showed increased markers of oxidative stress after nicotine conditioning for 2 and 3 days, while the CUMS further potentiated pro-oxidative effects of nicotine. Moreover, metyrapone reversed oxidative changes caused by stress and nicotine, while imipramine was not able to overwhelm nicotine- and stress-induced oxidative damages; however, it could exert antioxidant effect if administered repeatedly. The results suggest that recent exposure to a stressor may augment the rewarding effects of nicotine through anhedonia- and stress-related mechanisms. Our study contributes to the understanding of behavioral and biochemical stress-induced modification of the rewarding effects of nicotine on the basis of the development of nicotine dependence.
Highlights
Drug dependence is a global public health concern with major economic consequences worldwide
All rats showed no significant place preference for the drugassociated compartment before drug conditioning, which indicated that the conditioned place preference (CPP) procedure that we used was of an unbiased design
In the first series of experiments, we aimed to evaluate the relationship between nicotine administration and the chronic unpredictable mild stress (CUMS) in rats using the CPP paradigm widely used to study the rewarding effects of psychoactive substances
Summary
Drug dependence is a global public health concern with major economic consequences worldwide. Human and animal studies have identified stress as a critical factor in the drug addiction effects, including acquisition, retention, and relapse to drug abuse [1,2,3,4,5,6,7,8]. Clinical studies have demonstrated that exposure to stress or the presentation of stress-related cues can induce relapse to drug-seeking behavior in humans [9,10,11]. Stressful situations can increase alcohol intake in humans [10] In support of these clinical findings, animal studies report enhanced drug-induced reinstatement of cocaine and amphetamine self-administration and place conditioning or reinforcing properties of cocaine and drug-seeking behavior [13,14,15,16]. A great number of studies demonstrate that stress potentiates the rewarding
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