Oral administration of crocin significantly alleviated anxiety, and depressive-like behavior following ethanol and nicotine abstinence.

Oral administration of crocin significantly alleviated anxiety, and depressive-like behavior following ethanol and nicotine abstinence in adolescent male rats.

Samaneh Kakhki, Elham Fadavi Razdabi, Farnaz Mohammadzadeh, Ali Abbaszade-Cheragheali, Mahshid Jomehpour, Farimah Beheshti

Sci Rep

Sep 25, 2025

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Abstract

There are increasing concerns about nicotine (Nic) and ethanol (Eth) dependence and more importantly the detrimental effects of Nic abstinence among adolescents. The present study aims to assess the effects of crocin main constituent of saffron on anxiety, and depressive like behavior caused by withdrawal following co-abuse of Eth and Nic by assessing related behavioral and biochemical analysis. To this end, behavioral tests including elevated plus maze, open field and forced swimming tests alongside related biochemical analysis were done in which experienced abstinence or treated with crocin. Nic-Eth abstinence induced anxiety- and depressive-like symptoms, whereas both doses of crocin (20 and 30 mg/kg) decreased anxiety and depression induced by Nic-Eth abstinence. In biochemical analysis, crocin as well as buprenorphine-naloxone (Bup-Nal) improved the both oxidative/antioxidant and inflammatory/anti-inflammatory biomarkers balance. Furthermore, serotonin significantly increased in Nic-Eth group treated with either crocin or Bup-Nal. In addition, MAO activity significantly increased in Nic-Eth group, whereas treatment of that with crocin as well as Bup-Nal notably attenuated MAO activity. BDNF notably increased in Nic-Eth group treated with crocin and Bup-Nal. Considering previous results, crocin have a wide range of pharmacological effects, and the present findings also confirmed that it has strong potential to be effective in anxiety, and depressive-like behavior occurred in withdrawal following Nic and Eth.