Neurotransmitter interactions within the rat neostriatum

Crawford, Martin (1990) Neurotransmitter interactions within the rat neostriatum. University of Southampton, Doctoral Thesis.

Abstract

D-[³H] aspartate was taken up into crude striatal synaptosomes by a high affinity, sodium-dependent process characteristic of a neuronal neurotransmitter reuptake system. Uptake was increased following synaptosomal depolarization and both basal and depolarization-augmented uptake were modulated by the presence of dopamine. The use of specific antagonists implicated the involvement of both D1 and D2 receptors in these responses. [³H] glycine was found to be taken up into striatal slices by a high affinity, sodium-dependent system, again indicative or a neuronal neurotransmitter reuptake process. This uptake was increased following activation of either the NMDA, kainate or quisqualate subtype of excitatory amino acid receptor. Lesion studies localised the site of uptake to the terminals of the cortico-striatal pathway and not to intrinsic striatal neurones. Ca⁺⁺-dependent [³H] dopamine release from superfused striatal slices could be evoked using either high K⁺ or agonists at any of the above mentioned excitatory amino acid receptor subtypes. Although both cholinergic and GABAergic systems were involved in the control of striatal [³H] dopamine release, studies involving either TTX or striatal synaptosomes indicated that the excitatory actions of L-glutamate in this system were directly mediated. The existence of strychnine-insensitive glycine receptors specifically associated with the NMDA receptor complex was demonstrated. Activation of these receptors by glycine or D-serine was found to facilitate the [³H] dopamine releasing actions of NMDA. Such an enhancement could be competitively inhibited by HA-966 or kynurenate. Results obtained from lesion studies were indicative or a presynaptic, glutamate releasing action of the NMDA agonist biotenate, whilst DL-APB exerted partial agonist effects upon these glutamatergic terminals. The endogenous excitatory amino acid agonists cysteine and homocysteine as well as a novel tripeptide related to IgF1 were seen to augment [³H] dopamine release in this system, probably via actions upon NMDA receptors. [³H] glucine was released in a partially Ca⁺⁺-dependent manner from striatal slices with the release being facilitated by L-glu. This action was probably mediated via the APB-sensitive subtype of excitatory amino acid receptor since NMDA, kainate and AMPA were without effect here. The complex interactions which exist between dopamine, excitatory amino acids and glycine within the rat neostriatum are discussed.

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