Cocaine potentiates defensive behaviors related to fear and anxiety

Cocaine use has been associated with a number of psychiatric disturbances, and an emerging literature attests to its ability to enhance anxiety-like b ehaviors in animal models. Ethoexperimental analyses of defensive behaviors , and tests designed specifically to provide individual measures of these b ehaviors, have been shown to respond very selectively and appropriately to anxiolytic and panicogenic or panicolytic drugs, suggesting that these test s, and this approach, might provide a more detailed and comprehensive descr iption of the emotionality effects of cocaine than is currently available. In a Mouse Defense Test Battery (MDTB) using mouse subjects and an anesthet ized rat as the threat stimulus, cocaine consistently enhanced flight and e scape, with effects seen at 10-30 mg/kg (i.p.) dose levels. The effect was so potent that a lack of cocaine effect on other behaviors may have been du e to response competition, or to early distancing of cocaine-dosed subjects from the threat stimulus. In a Rat Runway Test (RRT) similar to the MDTB b ut with rat subjects, 4 mg/kg cocaine, i.v. produced an explosive, but well directed, flight response. Flight was still elevated, although of lesser m agnitude than originally, 30 min, after the i.v. cocaine, and defensive thr eat/attack to the oncoming threat stimulus were also reliably increased. Cocaine enhancement of defense was also seen in tests of sniffing "stereoty py" in rats. Sniffing after 30 mg/kg cocaine, i.p. was found to be appropri ately oriented toward the direction of incoming air flow, suggesting that i t may be part of a defensive risk assessment pattern. In undosed rats, risk assessment is suppressed by the presence of high-magnitude threat stimuli such as a cat, and the same, durable, phenomenon was obtained after 30 mg/k g (i.p.) cocaine. Toy cat exposure initially suppressed sniffing in cocaine -dosed rats, but this suppression was removed and sniffing increased, over repeated dose/toy cat exposures. Crouching in the same animals over these t esting regimes supported a "sniffing-suppression" interpretation of these c hanges and also provided data suggesting that cocaine may enhance crouching . These data, indicating that cocaine enhances a number of defensive behavior s-some more strikingly than others-have implications for the involvment of cocaine in defense-linked psychopathologies; and for the involvement of def ense in both conditioning and "sensitization" phenomena associated with coc aine. These effects raise the issue of the relationship between the defense -enhancing and the reinforcing consequences of cocaine. (C) 1999 Elsevier S cience Ltd. All rights reserved.