Temporal Memory Dysfunction and Alterations in Tyrosine Hydroxylase Immunoreactivity in Adult Rats Following Neonatal Exposure to Domoic Acid

摘要

The purpose of the present study was to determine whether early alterations in glutamate signaling, via daily injections of the glutamate agonist, domoic acid (DOM; 20 μg/kg), during a critical period of CNS development (PND 8 - 14), would result in temporal memory deficits and/or alterations in tyrosine hydroxylase (TH) immunoreactivity. As adults, subjects were assessed for temporal memory ability using a recency discrimination paradigm. Both number and duration of exploratory contacts directed at familiar objects, differing by one hour in recall delay, were measured. Analyses revealed that DOM-treated females demonstrated temporal memory dysfunction, as evidenced in a significantly lower proportion of total exploratory behaviour directed toward the remote object. Integrity of the dopamine system was assessed using immunohistochemistry to examine TH immunoreactivity in the prefrontal cortex (PFC) and nucleus accumbens (NAcc). Sections obtained from DOM-treated males had significantly less TH immunoreactivity in the right mPFC, while DOM-treated females had significantly greater TH immunoreactivity in the left core and right shell of the NAcc. These findings are discussed in context of early alterations to glutamate signaling in the development of human neuropsychiatric disorders.