Adaptive mechanisms following antidepressant drugs: Focus on serotonin 5-HT2A receptors

Background: There is a strong support for the role of serotonin (5-HT) neurotransmission in depression and in the mechanism of action of antidepressants. Among 5-HT receptors, 5-HT2A receptor subtype seems to be an important target implicated in the above disorder. Methods: The aim of the study was to investigate the effects of antidepressants, such as imipramine (15 mg/kg), escitalopram (10 mg/kg) and tianeptine (10 mg/kg) as well as drugs with antidepressant activity, including N-acetylcysteine (100 mg/kg) and URB597 (a fatty acid amide hydrolase inhibitor, 0.3 mg/kg) on the 5-HT2A receptor labeling pattern in selected rat brain regions. Following acute or chronic (14 days) drug administration, rat brains were analyzed by using autoradiography with the 5HT(2A) receptor antagonist [H-3]ketanserin. Results: Single dose or chronic administration of imipramine decreased the radioligand binding in the claustrum and cortical subregions. The [H-3]ketanserin binding either increased or decreased in cortical areas after acute N-acetylcysteine and URB597 administration, respectively. A similar shift towards reduction of the [H-3]ketanserin binding was detected in the nucleus accumbens shell following either acute treatment with imipramine, escitalopram, N-acetylcysteine and URB597 or repeated administration of imipramine, tianeptine and URB597. Conclusions: In conclusion, the present result indicate different sensitivity of brain 5-HT2A receptors to antidepressant drugs depending on schedule of drug administration and rat brain regions. The decrease of accumbal shell 5-HT2A receptor labeling by antidepressant drugs exhibiting different primary mechanism of action seems to be a common targeting mechanism associated with the outcome of depression treatment. (C) 2019 Maj Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.