Hyperprolactinemia impairs object recognition without altering spatial learning in male rats

Abstract

Prolactin (PRL) exerts protective effects on the hippocampus against chronic stress exposure, or kainic acid insults. Further, PRL null mice were recently shown to exhibit learning and memory deficits. These findings suggest the hippocampus as a PRL target. To test this hypothesis, we analyzed the hippocampal formation function in dependence of serum PRL concentrations. Male Sprague-Dawley rats were either transplanted with 2 pituitary homografts (HPRL) or had a sham operation (SHAM). Other groups were given vehicle (VEH) or daily injections of bromocriptine (BRC, 4mg/kg) to reduce PRL levels. The animals were sequentially subjected to the Morris water maze (MWM), the object recognition test and the elevated plus maze. PRL concentrations were measured with ELISAs. Learning curves from the MWM showed a progressive reduction in distance over time but no significant differences were found between SHAM and HPRL, or between BRC and VEH groups. Also, memory retrieval was not affected in the probe trial between each pair of groups. However, in the object recognition test the HPRL group failed to discriminate between novel and familiar objects, and the discrimination index was significantly reduced from that of the VEH group. BRC rats exhibited a reduced exploration of both objects compared to VEH, but had a discrimination index similar to VEH. No significant differences were observed in the EPM. In conclusion, high PRL levels impair object recognition but do not alter spatial learning. These results show for the first time that PRL impairs object recognition, and thus modulates non-spatial cognitive tasks.

Keywords: Bromocriptine; Cognition; Familiarity; Hippocampus; Morris water maze; Prolactin.