Release of endogenous excitatory amino acids in the neostriatum of the rat under physiological and pharmacologically-induced conditions

Abstract

There is immunohistochemical evidence suggesting that glutamate (Glu) is released from nerve terminals and acts, via several receptor subtypes, as a major excitatory neurotransmitter in the cortico-striatal pathway of the rat. Aspartate (Asp) is also present in cortico-striatal neurons, but its role as a neurotransmitter has been questioned, since, in contrast to Glu, it has not been demonstrated in presynaptic vesicles. Glu and Asp can be found at submicroM concentrations in the extracellular compartment of most areas of the basal ganglia. Their concentrations are largely regulated by transport mechanisms, but also by a synaptotagmin-dependent exocytotic release, and are sufficiently high to occupy junctional and extrajunctional receptors. We have investigated whether Glu and Asp release in the neostriatum can be selectively modulated by different neuronal systems. Dopamine (DA) and cholecystokinin (CCK) selectively stimulate Asp release, via D1 and CCKB receptor subtypes, respectively. Also opioid kappa-agonists increase Asp release. We propose that the selective modulation of Asp release by D1-, CCKB- and kappa-agonists involves striatal neurons containing Asp, but not Glu. In contrast, local perfusion with the mu-opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) increases both Glu and Asp release. This effect is probably exerted on cortico-striatal terminals, via presynaptic inhibitory mu-receptors. Thus, these results demonstrate that extracellular levels of Glu and Asp are modulated differentially by different neuronal systems, and suggest that in the neostriatum of the rat there are neuronal populations using Glu and/or Asp as messenger(s).

Intrinsic GABA neurons inhibit proenkephalin gene expression in slice cultures of rat neostriatum

“…It is also possible that the cortical afferents more directly activated the PEnk gene expression, whereas the intrinsic striatal expression was due to complex neuronal interactions in which AMPA receptors were involved. There is indeed some functional evidence that endogenous glutamate and/or aspartate is released in the striatum (Herrera‐Marschitz et al ., 1998), although the origin of the agonist is unclear.…”

Effect of prenatal and early life paracetamol exposure on the level of neurotransmitters in rats—Focus on the spinal cord

“…It is important to note as well, that this drug induces the release of opioid peptides and activates the spinal descending inhibitory system (Andersson et al, 2011). The local perfusion of kappa opioid receptor agonists stimulates the release of aspartate in the rat neostriatum (Herrera‐Marschitz et al, 1998).…”