Involvement of 5-HT1A receptors in the antidepressant-like effect of adenosine in the mouse forced swimming test.
This study investigated the involvement of 5-HT1 and 5-HT2 receptors in the antidepressant-like effect of adenosine in the mouse forced swimming test (FST). The pre-treatment of mice with PCPA (100mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5mg/kg, i.p., a 5-HT1A receptor antagonist), pindolol (32 mg/kg, i.p., a 5-HT1A/1B receptor/beta-adrenoceptor antagonist) or WAY100635 (0.1 and 0.3mg/kg, s.c., a selective 5-HT1A receptor antagonist), but not with ketanserin (5mg/kg, i.p., a 5-HT2A/2C receptor antagonist), prevented the antidepressant-like effect of adenosine (10mg/kg, i.p.) in the FST. Moreover, the pre-treatment of animals with WAY100635 (0.1mg/kg, s.c.) blocked the decrease in immobility time in the FST elicited by adenosine (5 or 10mg/kg, i.p.), but produced a synergistic effect with a sub-effective dose of adenosine (1mg/kg, i.p.) and did not cause any alteration at the highest dose of adenosine administered (50mg/kg, i.p.). Adenosine (1mg/kg, i.p.) produced a synergistic antidepressant-like effect with pindolol (32 mg/kg), NAN-190 (0.5mg/kg, i.p.), WAY100635 (0.03 mg/kg, s.c.), 8-OH-DPAT (1mg/kg, i.p., a 5-HT1A receptor agonist), but not with DOI (1mg/kg, i.p., a preferential 5-HT2A receptor agonist) or ketanserin. The pre-treatment of mice with DPCPX (2mg/kg, i.p., a selective adenosine A1 receptor antagonist) or ZM241385 (1mg/kg, i.p., a selective adenosine A2A receptor antagonist) did not prevent the effect of fluoxetine (32 mg/kg, i.p., a preferential serotonin reuptake inhibitor) in the FST. Besides that, adenosine (1mg/kg, i.p.) did not produce a synergistic antidepressant-like effect with fluoxetine (10mg/kg, i.p.). Taken together, the results indicate that the antidepressant-like effect of adenosine in the FST appears to be mediated, at least in part, by an interaction with 5-HT1A receptors.
Kaster
Manuella P
MP
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-900, SC, Brazil.
Santos
Adair R S
AR
Rodrigues
Ana L S
AL
D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004357:Drug Synergism; D005260:Female; D008297:Male; D051379:Mice; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013550:Swimming / Q000523:psychology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000241:Adenosine; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000928:Antidepressive Agents; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors