Long-Term Antidepressant Treatment Decreases Spiroperidol-Labeled Serotonin Receptor Binding

Abstract

Antidepressants compete at several neurotransmitter receptor binding site, but drug affinities do not correlate with clinical efficacy. Long-term, but not short-term, antidepressant treatment decreases the numbers of both serotonin and beta-adrenergic receptors. The decrease in the number of receptor sites is most marked for [3H]spiroperidol-labeled serotonin receptors and is characteristic for antidepressants of several classes.

The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

“…First and foremost, a number of placebo controlled trials have found that addition of drugs, which share a common pharmacological action of 5-HT 2 receptor blockade (eg, mianserin, mirtazapine and olanzapine), appear to enhance the antidepressant efficacy of SSRIs (Marek et al, 2003). Second, downregulation of 5-HT 2A receptors is a common and reasonably specific characteristic for known antidepressant drugs (Peroutka and Snyder, 1980), although some controversy exists regarding the effects of SSRIs. Third, a trend exists for upregulation of 5-HT 2A receptor binding in discrete prefrontal cortical regions of suicide victims from postmortem studies (Pandey et al, 2002;Stockmeier et al, 1997).…”

The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain

“…Currently in focus is the concept of Sulser et al (1978) which, like many of its predecessors, proposes an association between central noradrenergic activity and the depressed state: specifically, the mechanism underlying successful antidepressant therapy is desensitization of the central beta-adrenergic receptor-coupled adenylate cyclase system. Evidence that 5HT receptors are also down-regulated by TCA (Peroutka and Snyder, 1980;Sugrue, 1981) and that serotonergic innervation seems to play a permissive role in beta-adrenergic receptor desensitization (Brunello et al, 1982) supports the idea of an indoleamine-catecholamine link (Prange et al, 1974) and has resulted in further modification of this concept (Sulser, 1984a(Sulser, , 1984b.…”

Paradoxical trafficking and regulation of 5-HT2A receptors by agonists and antagonists

“…1B, Tables 1, 2, and 3). The paradoxical down-regulation of 5-HT 2A receptors was first described in in vivo studies of rats chronically treated with antidepressants by Bergstrom and Kellar in 1979 [4] and Peroutka and Snyder in 1980 [76]. Bergstrom and Kellar [4] demonstrated that chronic treatment with the antidepressant desipramine caused a reduction in serotonin binding sites in the cerebral cortex.…”

“…Bergstrom and Kellar [4] demonstrated that chronic treatment with the antidepressant desipramine caused a reduction in serotonin binding sites in the cerebral cortex. In more complete studies using a high affinity 5-HT 2A radio-labeled ligand, spiroperidol, Peroutka and Snyder [76], described statistically significant down-regulation of 5-HT 2A receptors in the frontal cortex of rats chronically treated with the tricyclic antidepressants amitryptiline, desipramine, and imipramine (Tables 1 and 2).…”

“…Additionally, serotonin-selective uptake inhibitors (SSRIs) have varying effects on 5-HT 2A down-regulation. For instance, depending on the study, fluoxetine has been reported to have either no effect on 5-HT 2A receptor number [15,40,41,76], or actually increase receptor number [52]. Similarly, paroxetine has also been reported to increase [15] or have no effect [3] on 5-HT 2A receptor numbers.…”