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.
Highlights
Glutamate (Glu) is the major excitatory neurotransmitter in the mammalian CNS and approximately half of all neurons in the brain are classified as glutamatergic [1]
We have previously demonstrated that chronic exposure to low doses of domoic acid (DOM; a selective KA receptors (KAR) agonist) during a critical period of brain development produces adult animals that demonstrate social withdrawal [12], deficient pre-pulse inhibition (PPI) [13] and latent inhibition (LI) [14], and increases in respon- siveness to novelty [15], which may arguably reflect negative, cognitive, and positive symptoms of schizo- phrenia, respectively
Prefrontal Cortex An analysis of immunoreactivity in the right medial prefrontal cortex (mPFC) of male rats revealed a statistically significant treatment effect with DOM-treated rats exhibiting less tyrosine hydroxylase (TH) staining than SAL-treated counterparts [t(9) = −2.392, p = 0.02] (Figure 2(b)), an effect not present in female DOMtreated rats (Figure 2(a))
Summary
Glutamate (Glu) is the major excitatory neurotransmitter in the mammalian CNS and approximately half of all neurons in the brain are classified as glutamatergic [1]. We have previously demonstrated that chronic exposure to low doses of domoic acid (DOM; a selective KAR agonist) during a critical period of brain development produces adult animals that demonstrate social withdrawal [12], deficient pre-pulse inhibition (PPI) [13] and latent inhibition (LI) [14], and increases in respon- siveness to novelty [15], which may arguably reflect negative, cognitive, and positive symptoms of schizo- phrenia, respectively These observations, in conjunction with additional previously published data from our labo- ratory suggesting that early postnatal exposure to low-doses of DOM produce alterations in the functional in- tegrity of the mesocorticolimbic pathway [15,16,17] and altered cognitive functioning [17], are largely consistent with both clinical manifestations of schizophrenia and with those changes reported in existing animal models [18,19,20,21,22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
