Involvement of 5-HT 1A receptors in the antidepressant-like effect of adenosine in the mouse forced swimming test

Abstract

This study investigated the involvement of 5-HT 1 and 5-HT 2 receptors in the antidepressant-like effect of adenosine in the mouse forced swimming test (FST). The pre-treatment of mice with PCPA (100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT 1A receptor antagonist), pindolol (32 mg/kg, i.p., a 5-HT 1A/1B receptor/β-adrenoceptor antagonist) or WAY100635 (0.1 and 0.3 mg/kg, s.c., a selective 5-HT 1A receptor antagonist), but not with ketanserin (5 mg/kg, i.p., a 5-HT 2A/2C receptor antagonist), prevented the antidepressant-like effect of adenosine (10 mg/kg, i.p.) in the FST. Moreover, the pre-treatment of animals with WAY100635 (0.1 mg/kg, s.c.) blocked the decrease in immobility time in the FST elicited by adenosine (5 or 10 mg/kg, i.p.), but produced a synergistic effect with a sub-effective dose of adenosine (1 mg/kg, i.p.) and did not cause any alteration at the highest dose of adenosine administered (50 mg/kg, i.p.). Adenosine (1 mg/kg, i.p.) produced a synergistic antidepressant-like effect with pindolol (32 mg/kg), NAN-190 (0.5 mg/kg, i.p.), WAY100635 (0.03 mg/kg, s.c.), 8-OH-DPAT (1 mg/kg, i.p., a 5-HT 1A receptor agonist), but not with DOI (1 mg/kg, i.p., a preferential 5-HT 2A receptor agonist) or ketanserin. The pre-treatment of mice with DPCPX (2 mg/kg, i.p., a selective adenosine A 1 receptor antagonist) or ZM241385 (1 mg/kg, i.p., a selective adenosine A 2A 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 (1 mg/kg, i.p.) did not produce a synergistic antidepressant-like effect with fluoxetine (10 mg/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-HT 1A receptors.