Mitigation of addictive effects induced by lorazepam through concurrent administration of SSRI: Interplay of serotonin and dopamine in caudate and nucleus accumbens

The present study aimed to assess the antidepressant profile of fluoxetine in the rats exhibiting lorazepam-induced abusive effects in place preference paradigm. Lorazepam, a benzodiazepine is commonly utilized for treating anxiety, panic attacks, status epilepticus, depressive disorders and sedation. Despite its therapeutic benefits, repeated lorazepam administration can lead to dependence, possibly involving heightened dopaminergic neurotransmission. Additionally, an important role is played by serotonergic system in anxiety and addiction pathophysiology and treatment. The study aimed to examine fluoxetine's impact on lorazepam-induced addiction, as fluoxetine, a selective serotonin reuptake inhibitor, enhances 5-HT availability by inhibiting its reuptake in neurons. Behavioral parameters, including growth rate, food intake, behaviors in forced swim test, open field, light dark box test, Skinner’s box and conditioned place preference, were monitored in rats subjected to oral lorazepam (2 mg/kg) and fluoxetine (1mg/kg) administration. Neurochemical analysis suggests that fluoxetine enhances serotonin levels, which counteracts the dopamine-driven addictive effects of lorazepam within the caudate and nucleus accumbens. This supports the notion that serotonin-dopamine interplay facilitates mitigate dependency by stabilizing the reward pathways following lorazepam administration.