Date of Completion

Spring 5-13-2019

Project Advisor(s)

John D. Salamone

University Scholar Major



Behavioral Neurobiology


Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) are the most commonly prescribed treatments for depression. Although efficacious for symptoms such as a depressed mood, SSRIs do not alleviate symptoms of amotivation, anergia, and fatigue. Furthermore, in clinical and preclinical studies, SSRIs have been shown to exacerbate motivational impairments and general fatigue. It is likely that fluoxetine-induced dysfunctions are due to overstimulation of one or more 5-HT receptors, with one possible candidate being the 5-HT1B receptor. Therefore, the aim of the study was to evaluate the role of 5-HT1BRs in fluoxetine-induced amotivation using a rodent behavioral model of effort-based decision-making. For these experiments, the selective 5-HT1BR antagonist, NAS-181, was co-administered with fluoxetine to determine if fluoxetine-induced suppression of high effort behavior could be attenuated. NAS-181 partially reversed the effects of fluoxetine in rats that showed a greater fluoxetine-induced behavioral suppression in our task, which was not found in rats with low fluoxetine-induced suppression. Future directions involve intracranial administration and investigation of the role of other 5-HTRs on effort-related behaviors.