MODULATION OF 5-HT RELEASE IN THE GUINEA-PIG BRAIN FOLLOWING LONG-TERM ADMINISTRATION OF ANTIDEPRESSANT DRUGS

被引:105
作者
BLIER, P
BOUCHARD, C
机构
[1] Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, H3A 1A1, 1033, Pine Avenue West
关键词
5-HT REUPTAKE BLOCKADE; MONOAMINE OXIDASE INHIBITION; 5-HT AUTORECEPTOR; ALPHA(2)-ADRENOCEPTORS; 5-HT; RECEPTORS; H-3] 5-HT RELEASE; H-3] NORADRENALINE RELEASE;
D O I
10.1111/j.1476-5381.1994.tb17015.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 [H-3]-5-HT, and to assess the sensitivity of the terminal 5-HTID autoreceptor, the alpha(2)-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 alpha(2)-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 [H-3]-5-HT. The paroxetine treatment did not alter the sensitivity of this alpha(2)-adrenoceptor in the hypothalamus. 5 The sensitivity of the alpha(2)-adrenoceptor on noradrenaline terminals, also assessed using UK 14.304, was not altered in hippocampus and hypothalamus slices preloaded with [H-3]-noradrenaline following the long-term befloxatone treatment. 6 In frontal cortex slices, [H-3]-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 [H-3]-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.
引用
收藏
页码:485 / 495
页数:11
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