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...

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In both humans and animals certain individuals seek stimuli or situations that are considered stressful and consequently avoided by others. A common feature of such situations is an activation of the hypothalamo-pituitaryadrenal axis leading to secretion of glucocorticoids. Since glucocorticoids have euphoric effects in some individuals and have been shown to potentiate the reinforcing properties of drugs of abuse in animals, we hypothesized that corticosterone secretion during stress-like situations may have reinforcing effects and that a higher sensitivity to the reinforcing effects of glucocorticoids might be a biological basis of sensation seeking. In this report we show that (a) corticosterone has reinforcing properties, as evidenced by the development of intravenous self-administration, (d) self-administration of corticosterone is observed at plasma levels that are comparable to those induced by stress, and (iii) there are individual differences in corticosterone self-administration, which are related to individual reactivity to novelty and sensitivity to drugs of abuse, behavioral features akin to certain traits of high-sensation seekers. These rmdings provide insight into the physiological role of glucocorticoids and the biology of sensation seeking and may have clinical implications.Avoidance is the usual response to stressful situations. However, certain individuals appear to seek situations involving a strong activation accompanied by a degree of stress that are generally avoided by others. "Stress-seeking" behavior has been described in various animal species. For example, in the monkey, Barrett and Spealman (1) have shown that high and constant rates of responding may be maintained on a lever that delivers electric shocks. In rats, it has been reported that a mild stress such as intense handling can induce place preference (2), a behavioral response commonly seen with drugs of abuse, and that certain subjects electrically self-stimulate aversive brain regions, inducing behavioral and autonomic disturbances similar to those of physiological stress (3). Seeking activating or stressful situations, like exposure to novelty in the rodent, has interesting adaptive correlates. Some rats exhibit a high locomotor reactivity when forced to a novel environment (4) or a high preference for novelty when given the choice between a familiar and a novel environment (5). These animals, defined as high responders (HRs) as opposed to low responders (LRs), also show a higher sensitivity to the behavioral and neurochemical effects of psychostimulants (4, 6) and a higher predisposition to self-administer this class of drugs intravenously (4,7,8).To account for the appetitive properties of stressful and stimulating experience, it may be postulated that some of the The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. biological responses to stressful and activa...

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