AVP (4-8) improves concept learning in PFC-damaged but not hippocampal-damaged rats.
A position reversal task was used to test the memory-enhancing effects of the arginine vasopressin analog [pGlu4, Cyt6] AVP (4-8) at a dose of 1.5 microg/kg. Rats received either sham operations (SHM), medial prefrontal cortex lesions (PFC), or hippocampal lesions (HIP). The peptide was administered daily, via s.c. injection, 30 min prior to training to half of the animals in each group. As expected, all animals performed equally well on the initial position habit and the first reversal. Overall, it was found that AVP (4-8)-treated animals performed significantly better across trials than saline (SAL)-treated animals. Further analysis showed that PFC animals that received AVP (4-8) (PFC+AVP) performed significantly better (at the level of controls) across trials than saline-treated PFC (PFC+SAL) animals. Sham animals that received the AVP (4-8) analog (SHM+AVP) only showed significant improvement on the last two reversals when compared to the sham saline-treated animals (SHM+SAL), which was likely due to a ceiling effect as performance reached high levels early in the reversal task. Trial 2 analysis across reversals revealed enhanced cognitive abilities in both sham groups (SHM+SAL, SHM+AVP) and the PFC+AVP group, but not in the PFC+SAL, HIP+AVP or the HIP+SAL groups. Hippocampal lesioned animals performed poorly on the task and injections of AVP (4-8) did not improve their performance. It is thus concluded that AVP (4-8) enhanced the acquisition of concept learning (win-stay/loose-shift) in this paradigm in PFC-damaged animals and ameliorated the perseverance habit that is often seen in PFC animals on this task. It is suggested that AVP (4-8) might have an enhancing effect on general cognitive abilities that is not limited to memory processes.