Effects of Tetrabenazine on Temporal Parameters of High-Effort Behaviors in Male and Female Rats

Motivational symptoms, such as fatigue and anergia, are common in various psychiatric and neurological disorders, including Parkinson’s disease and multiple sclerosis. These symptoms have been associated with dopamine (DA) levels in which DA depletion or antagonism has been linked to decreases in the selection of high-effort behaviors. For example, the DA-depleting agent tetrabenazine (TBZ) induces depressive symptoms in humans and depressive-like symptoms in rodents. To better understand the effects of TBZ on effortful behaviors, the current study examined the effects of TBZ on both the acquisition and the detailed temporal characterizations of high-effort behavior in male and female rats. During initial training (fixed ratio (FR)-1; FR-20; FR-40), males pressed more than females only during one week of FR-20 training, but this difference disappeared as the training continued. Upon completion of the initial training, rats received either TBZ (1.0 mg/kg for males, 2.0 mg/kg for females) or vehicle in two consecutive weeks. TBZ reduced FR-40 lever pressing compared to vehicle in both males and females. A detailed analysis on temporal parameters showed that TBZ increased inter-response times (IRTs) and post-reinforcement pauses (PRPs), indicating a slowing of response rates. We did not observe any sex differences in the lever pressing numbers or the temporal parameters with TBZ administration. These findings highlight the role of DA in motivational dysfunction and may help us understand how DA depletion affects high-effort behaviors and how it relates to motivational deficits that are seen in psychiatric disorders.