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 behaviors in animal models. Ethoexperimental analyses of defensive behaviors, and tests designed specifically to provide individual measures of these behaviors, have been shown to respond very selectively and appropriately to anxiolytic and panicogenic or panicolytic drugs, suggesting that these tests, and this approach, might provide a more detailed and comprehensive description of the emotionality effects of cocaine than is currently available. In a Mouse Defense Test Battery (MDTB) using mouse subjects and an anesthetized rat as the threat stimulus, cocaine consistently enhanced flight and escape, 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 due 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 but with rat subjects, 4 mg/kg cocaine, i.v. produced an explosive, but well directed, flight response. Flight was still elevated, although of lesser magnitude than originally, 30 min. after the i.v. cocaine, and defensive threat/attack to the oncoming threat stimulus were also reliably increased. Cocaine enhancement of defense was also seen in tests of sniffing "stereotypy" in rats. Sniffing after 30 mg/kg cocaine, i.p. was found to be appropriately oriented toward the direction of incoming air flow, suggesting that it 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/kg (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 testing regimes supported a "sniffing-suppression" interpretation of these changes and also provided data suggesting that cocaine may enhance crouching. These data, indicating that cocaine enhances a number of defensive behaviors--some more strikingly than others--have implications for the involvement of cocaine in defense-linked psychopathologies; and for the involvement of defense in both conditioning and "sensitization" phenomena associated with cocaine. These effects raise the issue of the relationship between the defense-enhancing and the reinforcing consequences of cocaine.