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© Copyright 2003 The British Pharmacological Society

016P University of Bristol
1st Focused Meeting April 2003

Effect of chronic electroconvulsive shock and antidepressant drug treatment on VGluT1 mRNA expression in rat brain regions

R. Tordera, M. Sprakes, Q. Pei, P. Burnet & T. Sharp.
University Dept. of Pharmacology, Oxford, OX1 3QT, U.K.


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Tordera R
Sprakes M

Pei Q
Sharp T

Recently, three isoforms of a vesicular glutamate transporter (VGluT1, VGluT2 and VGluT3) have been identified (Takamori et al., 2000; Herzog et al., 2001; Gras et al., 2002). Of these, VGluT1 is highly expressed in telencephalic regions where it is selectively located on synaptic vesicles in axon terminals making asymetric synapses (Fujiyama et al., 2001). VGluT1 is therefore expected to be a biochemical marker for excitatory glutamatergic neurones. Here we have studied the effect of repeated electroconvulsive shock (ECS) and antidepressant treatment on the mRNA levels of VGluT1.

Male Sprague-Dawley rats (250-270g) were used in all experiments. For chronic ECS treated groups, rats received a total of 5 shocks via ear clip or sham over 10 days under halothane anaesthesia. Separate groups of animals were given saline, paroxetine (5 mg/kg, i.p.), fluoxetine (5 mg/kg, i.p.) or desipramine (5 mg/kg, i.p.) twice daily for 14 days. Rats were killed 20 h after the last treatment. Brains were then processed for measurement of VGluT1 mRNA using in situ hybridization (Pei et al., 2000) with a 35S-labelled oligonucleotde probe (5'-GCACTGGGCACAAGGGAAGACTTGCATCTT-3'), (Herzog et al., 2001). VGluT1 mRNA abundance was determined by densitometric quantification of autoradiograms, and expressed as % of control.

High levels of specific labelling for VGluT1 mRNA was detected in the cerebral cortex including frontal, cingulate, orbital and parietal cortices, and different regions of the hippocampus as described previously (Herzog et al., 2001).

Table 1. Effect of chronic ECS, paroxetine, fluoxetine and desipramine on the mRNA abundance of VGluT1 in rat brain regions.

Frontal
Parietal
CA1
Dentat
Cortex
Cortex
Gyrus
         
Sham
100±3
100±2
100±3
100±3
ECS
112±3a
93±5
97±3
125±3b
Saline
100 ±13
100 ± 9
100±7
100 ± 11
Paroxetine
153±12 a
143±16
160±12b
140±10b
Fluoxetine
150±15 a
117±13
154±10b
148±13b
Desipramine
167±10 b
154±6a
161±11b
136 ± 9a

Data are mean ± s.e.m. values (n=6) expressed as % of control.ap<0.05; bp<0.01 vs saline or sham (one-way ANOVA followed by Dunnett's t-test).

Both chronic ECS and antidepressant treatment significantly increased VGluT1 mRNA abundance in the frontal cortex and in the dentate gyrus. The antidepressant drugs also increased VGluT1 mRNA in the CA1 region of the hippocampus (Table 1).

These data suggest that repeated ECS and antidepressant drugs increase the expression of VGluT1 in cortical and hippocampal regions of the rat brain.

Fujiyama F., et al., (2001) J. Comp. Neurol. 435: 379-387.
Gras C., et al., (2002) J. Neuroscience 22:5442-5451.
Herzog E., et al., ( 2001) J. Neuroscience 15, 21:RC181.
Pei Q., et al., (2000) Neuropharmacology 39: 463-470.
Takamori S., et al., (2000) Nature 407:189-194.