Excitatory Amino Acids Interaction and Neurotoxicity

It is supposed that Glu, and OXY are synthesized and stored in the same structure and parts of the brain. Both Glu and its receptors are located in different neurosecretory nuclei of the hypothalamus which are associated with neuroendocrine function. It have been demonstrated the presence of Glu in nucleus Paraventricularis (PVN), nucleus Ventro-Medianus (VMN), nucleus arcuatus, nucleus Supraopticus (SON), eminentia mediana and infundibulum of hypophysis [6]. In the pituitary gland Glu was found in pituicytes and terminal axons of hypothalamic neurosecretory cells reaching to the posterior pituitary [7]. Moreover mGluRs have been detected in different regions of hypothalamus and pituitary three parts [8], and expression of the gene GLU mainly in the vicinity of hypothalamic related with the regulation of neuroendocrine activities. Distribution of mGluR in area relevant to process of reproduction and neuroendocrine activities may be the main role of Glu in the regulation of these phenomena (OXY is synthesized primarily in giant nuclei neurons of the PVN and SON of hypothalamus) [9]. Additional evidence of the interaction between Glu and OXY derived from animal studies. Pampillo et al [10] have shown that in adult male rats Glu regulates the release of hypothalamic OXY by mGluR stimulation and excitation of cAMP signal transduction. Similarly Morsetta et al [11] demonstrated that mGluR stimulation increases the in vitro release of OXY from rat hypothalamic-pituitary tissue sections. Studies conducted on animals treated with phencyclidine specific antagonist of ion channels of NMDARs exhibit inhibition of prepulse. This is similar to the neurological situation in which a weak impulse inhibits the body’s reaction to a stimulus, respectively stronger, what was found in adult schizophrenics. Data concerning schizophrenia and other psychiatric disorders, may also suggest a link between Glu and OXY [12]. Long-term use of phencyclidine in male rats resulted in shortening the time to establish social and societal relationships [13]. There is still unknown mechanism which would explain the changes in social behavior caused by the drug, but it seems that the principal mediator of such behavior in rodents is the endogenous OXY. Studies performed by Caldwell et al [14] appear to confirm this hypothesis. In model of OXY knockout mice phencyclidine treatment increases prepulse inhibition in comparison to wild-type mice, what suggest that OXY is a natural antipsychotic compound. In addition Le et al [15] demonstrated that long-term use of phencyclidine in rats inhibits transcription of oxytocin mRNA in PVN of the hypothalamus and significantly reduce the OXY uptake by receptors. Moreover, OXY therapy returns social behavior inhibited by chronic use of phencyclidine.