Britton, Paul; (1994) Effect of tetanus toxin on extracellular levels of neuroactive amino acids and monoamines in rat hippocampus. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The effect of the neurotoxin tetanus toxin, unilaterally injected into the ventral hippocampal formation, on extracellular levels of neuroactive amino acids and monoamines was investigated in rats using intracerebral microdialysis. A single dose (1000 mouse minimum lethal doses) of tetanus toxin did not alter extracellular levels of aspartate, glutamate, and taurine 1, 2, 3, and 7 days after treatment. However, whilst extracellular GAB A levels were unaffected by toxin injection 1, 2, and 3 days after treatment, they were reduced (45% of contralateral vehicle injected level) at day 7. Toxin treatment caused a progressive decline in extracellular 5-hydroxytryptamine levels over the first 3 days of dialysis (20% of contralateral control level at day 3), and a 65% reduction 7 days after injection. Two days after toxin treatment dialysate dopamine level was elevated approximately 2-fold. However, by day 7 dopamine level was reduced by 54%. The 5-hydroxytryptamine metabolite, 5 -hydroxyindoleacetic acid declined in a manner similar to that of 5-hydroxytryptamine, but to a lesser extent, over the duration of investigation. Of the dopamine metabolites, extracellular 3,4- dihydroxyphenylacetic acid was decreased 2, 3, and 7 days after treatment, whilst homovanillic acid was not altered during the study. Seven days after treatment, challenge with high K+ produced increases in extracellular levels of taurine, GABA, 5-hydroxytryptamine, and dopamine in both vehicle- and toxin-treated hippocampi, with evoked levels of GABA, 5-hydroxytryptamine, and dopamine being lower in toxin-treated sides. At this time, an increase in the binding of [3H]-GABA to GABAA sites in the ventral CA1 pyramidal cell layer, and GABAB sites in the ventral CA1 and CA2 pyramidal cell layers was observed in toxin treated hippocampi. In contrast, [3H]-paroxetine binding density was decreased in ventral CA1 and CA3 pyramidal cell layers, and in the occipital cerebral cortex. It is proposed that tetanus toxin-induced behavioural and neuropathological effects may be related to reductions in extracellular levels of 5-hydroxytryptamine and GABA, respectively.

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