TITLE:
Temporal Memory Dysfunction and Alterations in Tyrosine Hydroxylase Immunoreactivity in Adult Rats Following Neonatal Exposure to Domoic Acid
AUTHORS:
Mark A. Robbins, Catherine L. Ryan, Amber L. Marriott, Tracy Ann Doucette
KEYWORDS:
Domoic Acid; Glutamate; Schizophrenia; Animal Models; Neurodevelopmental Disorders
JOURNAL NAME:
Neuroscience and Medicine,
Vol.4 No.1,
March
6,
2013
ABSTRACT: 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.