Effects of d-amphetamine on defensive behaviors related to fear and anxiety

In rodents, the administration of amphetamine has been associated with increased locomotor activity and stereotypy, and an emerging body of evidence suggests that it also enhances anxiety-like behavior in a number of animal models. Ethoexperimental analyses have outlined an array of defensive behaviors to threat that are responsive to anxiolytic, panicolytic-like and panicogenic agents, suggesting that the characterization of amphetamine effects on defense may provide further insights into the emotionality consequences of this drug.In Experiment 1, intraperitoneal administration of amphetamine (1 and 5 mg/kg, i.p.) on defensive behavior elicited by a predatory threat stimulus was assessed via time sampling analysis. Amphetamine dose-dependently suppressed freezing while potentiating locomotor activity. In Experiment 2, amphetamine was administered intravenously and animals were tested in a Rat Runway Test (RRT), designed to individually elicit a variety of defensive behaviors to a conspecific threat. All three doses of amphetamine (1, 2 and 5 mg/kg) produced robust changes in defensive responding by increasing directional flight behavior, jump escapes and upright/orientations. The results are in agreement with those of another psychostimulant, cocaine, and support a previously hypothesized link between flight and panic.