Withdrawal of caffeine after its chronic administration modifies the antidepressant-like activity of atypical antidepressants in mice. Changes in cortical expression of Comt, Slc6a15 and Adora1 genes

• Published in: Psychopharmacology 2018-08, Vol.235 (8), p.2423-2434
• Main Authors: Szopa, Aleksandra, Poleszak, Ewa, Doboszewska, Urszula, Herbet, Mariola, Świąder, Katarzyna, Wyska, Elżbieta, Serefko, Anna, Wlaź, Aleksandra, Korga, Agnieszka, Ostrowska, Marta, Juś, Piotr, Jedynak, Szymon, Dudka, Jarosław, Wlaź, Piotr
• Format: Article
• Language: English
• Subjects: Acetamides - pharmacology; Amino Acid Transport Systems, Neutral - metabolism; Analysis of Variance; Animals; Antidepressants; Antidepressive Agents - pharmacology; Antidepressive Agents, Second-Generation - pharmacology; Biomedical and Life Sciences; Biomedicine; Caffeine; Caffeine - pharmacokinetics; Caffeine - pharmacology; Catechol; Catechol O-methyltransferase; Catechol O-Methyltransferase - metabolism; Cerebral cortex; Cerebral Cortex - metabolism; Depression (Mood disorder); Gene Expression Regulation - drug effects; Hypnotics and Sedatives - pharmacology; Locomotion - drug effects; Locomotor activity; Male; Mental depression; Methyltransferase; Mianserin; Mianserin - pharmacology; Mice; mRNA; Neurosciences; Original Investigation; Pharmacology/Toxicology; Psychiatry; Psychological research; Psychopharmacology; Receptor, Adenosine A1 - metabolism
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-018-4940-6

Rationale Depressed patients often present increased consumption of caffeine. Objectives We aimed to investigate the effects of chronic treatment with caffeine (5 mg/kg, twice daily for 14 days) on the activity of single, ineffective doses of agomelatine (20 mg/kg) or mianserin (10 mg/kg) given on day 15 alone or simultaneously with caffeine. Methods We used the forced swim test (FST), tail suspension test (TST), and locomotor activity test in mice and quantitative real-time PCR analysis of the selected genes in the cerebral cortex (Cx). Results There were no changes in the immobility time between mice that received saline and caffeine for 14 days. Administration of agomelatine or mianserin on day 15 did not produce an antidepressant-like effect, but such effect was observed after administration of agomelatine or mianserin simultaneously with caffeine on day 15, in both mice that received saline and caffeine for 14 days. In mice treated with caffeine for 14 days, joint administration of agomelatine or mianserin and caffeine on day 15 decreased solute carrier family 6, member 15 ( Slc6a15 ), messenger RNA (mRNA) level in the Cx, compared to the group which received only the respective antidepressant on this day. Moreover, in mice treated with caffeine for 14 days, joint administration of mianserin and caffeine on day 15 decreased adenosine A1 receptor ( Adora1 ) and catechol- O -methyltransferase ( Comt ) mRNA level in the Cx, compared to the group which received mianserin without caffeine on this day. Conclusions Withdrawal of caffeine after its chronic intake can modify the activity of antidepressants. Adora1 , Slc6a15 , and Comt may be involved in the antidepressant-like effect observed after joint administration of caffeine and mianserin or agomelatine, following chronic treatment with caffeine.