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The effect of intracerebroventricular injection of insulin-like growth factor-1 on morphine-induced conditioned place preference extinction and reinstatement; a behavioral and biochemical experimental study

Erfan Ghadirzadeh,Mobina Gheibi,Ali Siahposht-Khachaki,Ehsan Vahdati Helan,Mohammad Farvardin,Shiva Shadi,Ali Abdolkarimi

Published 2025 in Behavioral and Brain Functions

ABSTRACT

Morphine addiction is a growing problem with severe consequences. Interestingly, Insulin-like Growth Factor-1 (IGF-1), a hormone with the ability to modulate neural pathways and exert neuroprotective and regenerative properties, could emerge as a potential treatment. However, to the best of our knowledge, the role of IGF-1 in the extinction and reinstatement phases of morphine induced conditioned place preference (CPP) remains unexplored. Thus, this study aimed to investigate the behavioral and biochemical effects of intracerebroventricular (ICV) IGF-1 administration on extinction and reinstatement after morphine induced CPP and c-Fos expression in nucleus accumbens (NAc). Rats were conditioned with morphine (5 mg/kg, subcutaneously). The study examined alterations in CPP scores after administering varying multiple doses of IGF-1 (5, 10, and 20 µg) daily during the extinction and reinstatement phases of CPP, or single 20 µg dose administration prior to the extinction or prior to the reinstatement phase. Following these procedures, c-Fos levels in the NAc were quantified using the ELISA method. The findings revealed that daily administration of IGF-1 at doses of 5, 10, and 20 µg resulted in a dose-dependent reduction in conditioning scores and shorter extinction period. Importantly, only the 20 µg attenuated morphine reinstatement significantly. Additionally, c-Fos levels, which increased following morphine exposure, were markedly reduced by IGF-1 administration across all phases. This study demonstrates that IGF-1 administration could facilitates the extinction and attenuate the reinstatement of morphine-induced CPP, highlighting its potential as a therapeutic strategy in opioid addiction.

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