Aged neuropeptide Y transgenic rats are resistant to acute stress but maintain spatial and non-spatial learning.

The behavioral phenotype of five-month-old rats overexpressing neuropeptide Y (NPY) has previously been described [Proc Natl Acad Sci USA 97 (2000) 12852]. In this transgenic rat model, there is central overexpression of prepro-NPY mRNA and NPY peptide in the hippocampus and hypothalamus and decreased Y1 binding sites within the hippocampus. These molecular and neurochemical events led to altered anxiety profile and learning abilities in NPY-overexpressing rats. In the present study, anxiety and learning/memory related behaviors were examined in one-year-old NPY-transgenic rats in order to assess any behavioral changes that may have occurred during the aging process. As observed in 5-month-old overexpressing rats, aged NPY-transgenic animals are resistant to acute physical restraint stress measured by the elevated-plus maze and demonstrate anxiolytic-like activity in the open field. However, in contrast to data in young rats, there was no significant difference between aged wildtype and NPY-transgenic animals in relation to spatial and non-spatial memory as indicated by the (allo- and ego-centric) Morris water maze and object recognition test. It would thus appear that the anxiolytic-like profile observed in young NPY-overexpressing rats is maintained in older animals providing further evidence for a role for NPY in anxious behaviors. However, the cognitive deficits observed in young rats do not appear to occur in older animals suggesting the existence of compensatory mechanisms leading to a reversal of the learning deficits noted in younger animals. These results also provide additional evidence for the mechanistic dissociation between anxiety and cognition-related behaviors modulated by NPY.