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Modulation of 5-HT release in the guinea-pig brain following long-term administration of antidepressant drugs

Corresponding Author

Pierre Blier

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033, Pine Avenue West, Montreal, Quebec, Canada H3A 1A1

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033, Pine Avenue West, Montreal, Quebec, Canada H3A 1A1Search for more papers by this author

Claude Bouchard,

Claude Bouchard

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033, Pine Avenue West, Montreal, Quebec, Canada H3A 1A1

Search for more papers by this author

Pierre Blier,

Corresponding Author

Pierre Blier

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033, Pine Avenue West, Montreal, Quebec, Canada H3A 1A1

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033, Pine Avenue West, Montreal, Quebec, Canada H3A 1A1Search for more papers by this author

Claude Bouchard,

Claude Bouchard

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033, Pine Avenue West, Montreal, Quebec, Canada H3A 1A1

Search for more papers by this author

First published: October 1994

https://doi.org/10.1111/j.1476-5381.1994.tb17015.x

Citations: 88

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Abstract

1
The aims of the present study were to determine whether long-term 5-hydroxytryptamine (5-HT) reuptake blockade and inhibition of type-A monoamine oxidase (MAO-A) lead to an enhancement of the electrically evoked release of tritium from guinea-pig brain slices preloaded with [₃H]-5-HT, and to assess the sensitivity of the terminal 5-HT_1D autoreceptor, the α₂-adrenoceptor also located on 5-HT terminals, and the 5-HT₃ receptor that modulates 5-HT release following these two types of antidepressant treatments.
2
The electrically evoked release of tritium was significantly enhanced following a 21-day treatment with the 5-HT reuptake blocker, paroxetine and the reversible MAO-A inhibitor, befloxatone, in preloaded slices of the hypothalamus, hippocampus and frontal cortex 48 h after removal of the osmotic minipumps used to deliver the drugs.
3
The inhibitory effect of the terminal 5-HT autoreceptor agonist, 5-methoxytryptamine, on the evoked release of tritium was attenuated in slices of the hypothalamus, hippocampus, but not frontal cortex, following the paroxetine treatment. In the befloxatone group, the effectiveness of 5-methoxytryptamine was unaltered in the same brain structures.
4
The sensitivity of the α₂-adrenoceptor on 5-HT terminals, assessed using UK 14.304, was attenuated in hypothalamus, hippocampus, but not frontal cortex slices prepared from befloxatone-treated guinea-pigs and preloaded with [₃H]-5-HT. The paroxetine treatment did not alter the sensitivity of this α₂-adrenoceptor in the hypothalamus.
5
The sensitivity of the α₂-adrenoceptor on noradrenaline terminals, also assessed using UK 14.304, was not altered in hippocampus and hypothalamus slices preloaded with [₃H]-noradrenaline following the long-term befloxatone treatment.
6
In frontal cortex slices, [₃H]-5-HT uptake was no longer significantly attenuated after a 21-day treatment with paroxetine, whereas it was still markedly inhibited in hypothalamus slices. The enhancing effect of paroxetine on the evoked release of [₃H]-5-HT in the superfusion medium was no longer evident in frontal cortex slices of the paroxetine group. These data indicate that long-term 5-HT reuptake blockade desensitized the 5-HT transporter in the frontal cortex.
7
The capacity of the 5-HT₃ receptor agonist, 2-methyl-5-HT, to enhance the electrically evoked release of tritium was not altered in hypothalamus, hippocampus, and frontal cortex slices prepared from befloxatone-treated guinea-pigs, but was significantly attenuated in the paroxetine group also treated for 21 days. Following a 2-day paroxetine treatment, the enhancing effect of 2-methyl-5-HT on tritium release was unaltered in frontal cortex slices.

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Volume113, Issue2

October 1994

Pages 485-495

Modulation of 5-HT release in the guinea-pig brain following long-term administration of antidepressant drugs

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Modulation of 5-HT release in the guinea-pig brain following long-term administration of antidepressant drugs

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