Attention-deficit/hyperactivity disorder (
ADHD) is a pervasive neurobehavioral disorder. We previously demonstrated differential expression of some
isoforms of Homer, a family of scaffolding
proteins localized to the postsynaptic density of glutamatergic excitatory synapses, in the spontaneous hypertensive rat (SHR), which is the most frequently used animal model of
ADHD. Since these changes were observed in the prefrontal cortex (PFC), a critical structure in
ADHD, it was hypothesized that these Homer
isoforms may play a role in
ADHD. The present study aimed to extend these findings to the hippocampus, which has direct connections to the PFC and subserves attention and cognition, two functions that are disturbed in
ADHD. Hippocampal
mRNA and
protein expression of several Homer
isoforms were investigated in both SHR and control Wistar-Kyoto (WKY) rats using reverse transcription-polymerase chain reaction and Western blotting, respectively. Both
mRNA and
protein for
Homer 1a and Homer 2a/b, but not Homer 1b/c, were expressed at significantly lower levels in the hippocampus of SHR compared to WKY rats. The effects of
methylphenidate (MPH) on spatial learning and memory in SHRs were also examined using the Morris water maze and on hippocampal expression of Homer
isoforms. MPH improved spatial learning and memory and up-regulated hippocampal expression of
Homer 1a and Homer 2a/b, but not Homer 1b/c, in SHRs. The animal model of
ADHD may have altered expression of
Homer 1a and Homer 2a/b in the hippocampus, in addition to the PFC. Future studies will focus on elucidating the specific mechanisms of
Homer 1a and Homer 2a/b in
ADHD.