Coenzyme Q10 ameliorates anxiety and depression‑like behavior associated with chronic opioid use and increases GDNF expression in the hippocampus of morphine‑dependent rats

Abstract

Opioid dependence is strongly associated with moderate to severe depression and anxiety. The primary objective of this investigation was to determine whether coenzyme Q10 (CoQ10) has the capacity to increase the level of glial cell line‑derived neurotrophic factor (GDNF), with the aim of ameliorating anxiety‑ and depression‑like behaviors in morphine (MOP)‑dependent rats. In this study, 40 male Wistar rats were randomly divided into five experimental groups: Oil group, MOP+Oil group, MOP+Q10‑100 group, MOP+Q10‑200 group, and MOP+Q10‑400 group. Rats received escalating doses of MOP (25 to 100 mg/kg, s.c.) once daily. After 21 days of drug dependency, CoQ10 was administered orally at doses of 100, 200, and 400 mg/kg once daily for four weeks. Behavioral assessments were conducted using the open field test, elevated plus maze, and forced swim test. GDNF expression in the hippocampus was evaluated using immunohistochemistry. Four weeks of CoQ10 treatment significantly improved anxiety‑ and depression‑like behaviors induced by MOP administration. Furthermore, CoQ10 significantly increased GDNF expression in the hippocampus. Oral administration of CoQ10 at doses of 100, 200, and 400 mg/kg over four weeks significantly reduced depressive‑ and anxiety‑related behaviors associated with prolonged MOP exposure. These behavioral improvements were accompanied by increased hippocampal GDNF expression.