No abstract

Individual vulnerability to the reinforcing properties of drugs appears to be an essential characteristic predisposing humans to addiction. In animals, a greater behavioral reactivity to a mild stress, such as exposure to a novel environment, is an index of the vulnerability to acquire amphetamine self-administration. Biological responses to stress as well as behavioral reactivity may predict such a vulnerability. In the present study, rats with a longer duration of corticosterone secretion after exposure to novelty showed facilitation of acquisition of amphetamine self-administration. Furthermore, corticosterone administration in nonpredisposed individuals increased the reinforcing value of the drug and facilitated the acquisition of amphetamine self-administration. These results indicate that the stress-related activity of the hypothalamicpituitary-adrenal axis may play a role in the pathogenesis of psychostimulant addiction.Individual differences to the reinforcing effects of the drugs (1) are considered by clinicians to be central to the etiology ofaddiction (2, 3). However, this aspect ofaddiction has been largely neglected in experimental studies using intravenous self-administration (SA) as a model ofdrug-taking behavior in animals. Nevertheless, when SA is studied during the period of acquisition and low doses of drug are used, individual differences to the drug's reinforcing effects are readily observed (4, 5). The ability to predict individual vulnerability and select populations of rats with different risks for developing drug SA may represent a valuable methodology for investigation of the biological basis of predisposition to drug-seeking behavior.Recently, it has been reported (6) that a predisposition to develop amphetamine SA in animals may be predicted by the behavioral reactivity of the individual animal to exposure to a novel environment. Thus, rats with an higher noveltyinduced locomotor activity readily acquired amphetamine SA, whereas rats with the lower response did not. These results prompted a search for the biological substrate of SA vulnerability in the activity of the hypothalamic-pituitaryadrenal (HPA) axis, such as the secretion of corticosterone during stress. This choice was based on three main observations. First, corticosteroids are central to the control ofthe homeostatic disturbances induced by environmental stimulations and stress (7-9). Second, this hormone modifies the activity of the central nervous system (10-13). Third, dopaminergic (DA) neurons, whose activity influences SA behavior (14-15), have corticosterone receptors on the cell bodies (16).This study addressed two specific questions. (i) Could corticosterone secretion during stress predict amphetamine SA vulnerability? (ii) Could corticosterone levels modify individual sensitivity to amphetamine? To explore these questions, the secretion of corticosterone after exposure to novelty was measured in rats tested for sensitivity to amphetamine SA, and the effects of an experimentally induced increase of corticos...

No abstract