RELEASE OF ENDOGENOUS EXCITATORY AMINO-ACIDS IN THE NEOSTRIATUM OF THE RAT UNDER PHYSIOLOGICAL AND PHARMACOLOGICALLY-INDUCED CONDITIONS

There is immunohistochemical evidence suggesting that glutamate (Glu) is released from nerve terminals and acts, via several receptor subtyp es, as a major excitatory neurotransmitter in the cortico-striatal pat hway of the rat. Aspartate (Asp) is also present in cortico-striatal n eurons, but its role as a neurotransmitter has been questioned, since, in contrast to Glu, it has not been demonstrated in presynaptic vesic les. Glu and Asp can be found at sub mu M concentrations in the extrac ellular compartment of most areas of the basal ganglia. Their concentr ations are largely regulated by transport mechanisms, but also by a sy naptotagmin-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 mod ulated by different neuronal systems. Dopamine (DA) and cholecystokini n (CCK) selectively stimulate Asp release, via D-1 and CCKB receptor s ubtypes, respectively. Also opioid kappa=agonists increase Asp release . We propose that the selective modulation of Asp release by D-1-, CCK B- and kappa-agonists involves striatal neurons containing Asp, but no t Glu. In contrast, local perfusion with the mu-opioid antagonist D-Ph e-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 demonst rate that extracellular levels of Glu and Asp are modulated differenti ally by different neuronal systems, and suggest that in the neostriatu m of the rat there are neuronal populations using Glu and/or Asp as me ssenger(s).