Research articleThe expression of amphetamine sensitization is dissociable from anxiety and aversive memory: Effect of an acute injection of amphetamine

- Expression of amphetamine locomotor sensitization is not accompanied with anxiety.
- Low basal anxiety levels predict high increase in AMPH-induced locomotor activity.
- An increase in inter-trial interval attenuate the retrieval of EPM aversive memory.
- A single AMPH injection restore retrieval of EPM aversive memory.

The repeated administration of amphetamine can lead to locomotor sensitization. Although the repeated administration of amphetamine has been associated with anxiety and impaired working memory, it is uncertain if expression of amphetamine sensitization is associated with modifications of emotional memories. To address this issue, rats were injected once daily with amphetamine for five consecutive days (1.5 mg/kg). After four days of withdrawal, rats were delivered an acute amphetamine injection to assess the expression of sensitization. A single exposure to an elevated plus maze (EPM), 24 h after the last injection of amphetamine, showed that amphetamine sensitization is not accompanied by anxiety. Next, aversive memory was assessed using an 11 day inter-trial interval between the EPM Trial 1 and EPM Trial 2. Rats administered with saline showed a percentage of open arms time (% OAT) in Trial 2 that was comparable to Trial 1, demonstrating a reduction in the retrieval of aversive memory. However, rats sensitized after the EPM Trial 1 showed a significant decrease in the % OAT in Trial 2. Importantly, a decrease in the % OAT in Trial 2 compared to Trial 1 was also observed after a single injection of amphetamine 24 h before Trial 2. These results show a facilitation in the retrieval of aversive memory, and suggest that a previous amphetamine injection is enough to produce a protracted activation of neural circuits necessary for the retrieval of aversive memory.