Effects of pharmacological manipulation on neurotransmitter and other amino acid levels in the CSF of the Senegalese baboon Papio papio

Abstract

The concentrations of GABA, glutamate, aspartate, glycine, taurine, glutamine, asparagine and alanine were determined in the CSF of 10 Senegalese baboons (Papio papio) following initial ketamine anaesthesia and subsequent administration (4 h later) of different compounds known to alter either inhibitory or excitatory neurotransmission. Ketamine itself was apparently without effect as the administration of a second dose of ketamine did not significantly alter the levels of any of the amino acids studied, although GABA levels tended to decrease. The presence of haemolysed material in occasional samples was associated with high GABA, glutamate, aspartate, taurine and asparagine levels. Therefore only haemolysate-free samples were included for analysis. Of the compounds administered, γ-vinyl GABA had the most evident effect on CSF amino acid levels, increasing GABA (>5-fold) and decreasing glutamate (>50%), aspartate (40–50%), asparagine (20%) and alanine (30–35%) levels. The changes in GABA, glutamate and aspartate were still apparent 24 h post-γ-vinyl GABA administration. In contrast, sodium valproate did not significantly alter the CSF levels of any of the amino acids studied. Upon acute administration allylglycine decreased the CSF concentrations of GABA and alanine, but not glutamate. These alterations are unlikely related to the occurrence of allylglycine-induced convulsions (in 2 of 4 experiments) as electroconvulsive shock did not alter CSF amino acid levels. During the experimental period encompassing the allylglycine injection (8 weeks), basal (initial post-ketamine, pre-drug sample) amino acid levels were abnormal with large increases in glutamate, GABA, aspartate and taurine whereas asparagine levels were below the limit of detection. Diazepam administration was followed by a significant increase in taurine and a decrease in aspartate levels. Administration of MK-801 was associated with an increase in taurine levels, whereas GABA levels were low immediately after PCP. No other changes in CSF amino acids were observed after the NMDA-channel blockers. The present results suggest that the Papio papio is a useful model for studying the alterations in CSF amino acids following pharmacological manipulation of central neurotransmitter systems. GABA and glutamate levels appear to be the most sensitive to change. For compounds with a long onset and/or duration of action the amino acid levels should be measured over several hours post-drug administration.