The effects of yohimbine and amphetamine on fear expression and extinction in rats

Psychostimulants, such as yohimbine and amphetamine, can enhance learning and memory. Extinction of conditioned fear involves new learning, so we asked whether psychostimulants could enhance this learning. Previous work suggests that yohimbine facilitates extinction, using freezing as a fear measure. However, psychostimulant-induced alterations in locomotion can confound freezing measurements. Furthermore, the effects of amphetamine on fear extinction have never been examined.

We evaluated the effectiveness of yohimbine and amphetamine in enhancing fear extinction. In addition to freezing, we measured bar-press suppression, which is less sensitive to changes in locomotion. We asked: Do psychostimulants reduce fear during extinction training when drug is present? Does learning extinction with psychostimulants result in better extinction retention?

Rats received fear conditioning on day 1 followed by partial extinction training on days 2 and 3. Yohimbine (1.0, 2.0, or 5.0 mg/kg, i.p.), amphetamine (1.0 mg/kg, i.p.), or vehicle were injected prior to extinction on day 2.

Yohimbine dose-dependently reduced freezing during extinction training on day 2, whereas bar-press suppression was reduced at the highest dose only. When tested drug-free, yohimbine-treated rats showed equivalent levels of freezing and suppression to controls. Amphetamine also decreased freezing during extinction, but did not decrease suppression. During the drug-free test, there was no difference between amphetamine-treated rats and controls in either measure.

Although yohimbine and amphetamine are capable of decreasing freezing, neither drug strengthened retention of fear extinction. Based on these rodent findings, psychostimulants may not be suitable adjuncts to extinction-based therapies for the treatment of anxiety disorders.