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Papers of the Week

Papers: 18 May 2024 - 24 May 2024

2024 May 21

Behav Brain Res


Low doses of acetaminophen produce antidepressive-like effects through the opioid system in mice.


Ghorbanzadeh B, Azizollahi B, Masoudipur F, Boron AR, Azizi M, Oroojan AA, Jafrasteh S


Acetaminophen (paracetamol) is one of the most popular analgesics for the management of fever and pain but few reports have investigated its antidepressant-like effect. Moreover, the role of the opioidergic pathway has been indicated in depression pathophysiology. This study aimed to examine the involvement of the opioid receptors in the antidepressant-like effect of acetaminophen after acute and sub-chronic administration using mice forced swimming test (FST). Our finding showed that administration of acetaminophen (50 and 100mg/kg, i.p.) 30min before the FST produced an antidepressant effect which was reduced by naloxone (1mg/kg, i.p., a nonselective opioid receptor antagonist). Moreover, we observed that acetaminophen in higher doses (200 and 400mg/kg) was ineffective. Also, the response of the non-effective dose of acetaminophen (25mg/kg) was potentiated by the non-effective dose of morphine (0.1mg/kg) in the FST that was antagonized by naloxone. Also, in contrast to morphine (10mg/kg), acetaminophen (100mg/kg, i.p.) induced neither tolerance to the anti-immobility behavior nor withdrawal syndrome after repeated administration. In addition, RT-PCR showed that hippocampal mu- and kappa-opioid receptor mRNA expression increased in mice after repeated administration of acetaminophen; however, morphine therapy for 6 days did not affect kappa-opioid receptor expression. Our findings demonstrated that acetaminophen in lower doses but not high doses revealed an antidepressant-like activity without inducing tolerance and withdrawal syndromes. Moreover, the observed effect of acetaminophen may be via altering the opioid system, particularly hippocampal mu- and kappa-receptors.