Spontaneous release of endogenous aspartate and glutamate from rat striatal slices is increased following destruction of local neurons by ibotenic acid

Abstract

We sought to determine in rat striatum whether the release of neurotransmitter amino acids aspartate (Asp), glutamate (Glu) and gamma-aminobutyric acid (GABA) were affected by local neurons. To do so, unilateral microinjections of ibotenic acid, and excitotoxin that destroys local neurons without affecting fibers of passage, were made into the striatum. Release of endogenous amino acids from lesioned and intact striatal slices were measured by HPLC one week later. The effectiveness and specificity of the lesion were confirmed by measuring the enzyme activity associated with extrinsic dopamine neurons (tyrosine hydroxylase; 111 +/- 14%), intrinsic GABA neurons (glutamic acid decarboxylase; 19 +/- 7%) and intrinsic acetylcholine neurons (choline acetyltranferase; 37 +/- 10%). Destruction of local striatal neurons markedly attenuated the release of GABA (41 +/- 12% of control) elicited by depolarization with K+ (35 mM), but did not significantly reduced the K+-evoked release of Asp (80 +/- 17%) and Glu (92 +/- 8%). However, spontaneous release of Asp and Glu was significantly greater than that observed in unlesioned tissue (159 +/- 18% and 209 +/- 27%, respectively), while the spontaneous release of GABA was not significantly reduced (75 +/- 43%). Although release of the neurotransmitter amino acids Asp, Glu and GABA were affected by the lesion, the release of the non-neurotransmitter amino acid tyrosine was unaffected. These data are consistent with the hypotheses that: 1) the predominant source of releasable stores of endogenous Asp and Glu in the striatum arises from extinsic neurons, and 2) that the spontaneous release of Asp and Glu from axon terminals in the striatum may be regulated, at least in part, by local inhibitory neurons.

Descending glutamatergic pathways of PFC are involved in acute and chronic action of methylphenidate

“…al., 1990; Kalivas and Stewart, 1991; Kalivas et. al., 1993), the role of PFC glutamatergic afferents in acute and chronic effects of MPD administration was studied via bilateral ibotenic acid infusions into PFC that selectively destroys the local glutamatergic neurons without disturbing other axon terminals (Arneri et. al., 1988).…”