Chronic fluoxetine treatment impairs motivation and reward learning by affecting neuronal plasticity in the central amygdala

Background and Purpose The therapeutic effects of fluoxetine are believed to be due increasing neuronal plasticity reversing some learning deficits. Nevertheless, a growing amount evidence shows adverse this drug on cognition forms plasticity. Experimental Approach To study the chronic treatment, we combine an automated assessment motivation in mice with investigation central amygdala basolateral amygdala. We use immunohistochemistry visualize types perineuronal nets, along DI staining assess dendritic spine morphology. Gel zymography is used test fluoxetine's impact matrix metalloproteinase-9, enzyme involved synaptic Key Results show that treatment non-stressed increases nets-dependent amygdala, while impairing MMP-9-dependent Further, illustrate how latter contributes anhedonia deficits reward learning. Behavioural impairments accompanied by alterations morphology spines towards immature state, most likely reflecting animals' inability adapt. strengthen link between its influence MMP-9 showing behaviour knockout animals remains unaffected drug. Conclusion Implications Chronic differentially affects various plasticity, possibly explaining opposing brain behaviour. These findings immediate clinical relevance since reported side pose potential threat patients.