Development of Physiological Markers for Tetrabenazine-Induced Motivational Dysfunctions Using Electroencephalography in Male and Female Rats

Depression is a mental illness that is increasingly rampant in our society. With its prevalence, various drugs have become commonplace for treatment. Many of these drugs are serotonin reuptake inhibitors, or SSRIs. These drugs are able to mitigate symptoms of depression such as rumination and anxiety. However, they are not very successful in treating the amotivation and anergia that are seen in these patients. In order to investigate which drugs will be the most successful in treating the symptoms of depression, it is important to develop an animal model that can accurately represent the motivational symptoms of depression in humans. The goal of the present study was to use female and male rats to develop electroencephalography (EEG) markers that can be readily translatable to the pathophysiology of female and male patients with depression. In this study, tetrabenazine (TBZ), a vesicular monoamine transporter-2 (VMAT-2) inhibitor, or a vehicle (VEH) control, was administered to a group of 8 female rats and 7 male rats prior to measuring EEG in the home cage. Recordings were taken from each treatment condition in the medial prefrontal cortex (mPFC), motor (M1/M2), and medial parietal (mParietal) cortices to investigate the effect of TBZ on these cortices and to determine whether they are comparable to the neurological markers associated with depression in humans. It was found that male rats demonstrated a predominant peak frequency at baseline in EEG activity across all three regions in the alpha/theta frequency range (4-12 Hz, with a sharp peak at 6-8.5 Hz frequency range). The sharp 6-8.5 Hz peak was suppressed when TBZ was administered in a 1.0 mg/kg dose. The EEG recordings of the female rats were not significantly affected. These findings can be used as a foundation to develop further EEG studies in behaving rats that can be translated to treatments for clinical depression within humans

Development of Physiological Markers for Tetrabenazine-Induced Motivational Dysfunctions Using Electroencephalography in Male and Female Rats

Depression is a mental illness that is increasingly rampant in our society. With its prevalence, various drugs have become commonplace for treatment. Many of these drugs are serotonin reuptake inhibitors, or SSRIs. These drugs are able to mitigate symptoms of depression such as rumination and anxiety. However, they are not very successful in treating the amotivation and anergia that are seen in these patients. In order to investigate which drugs will be the most successful in treating the symptoms of depression, it is important to develop an animal model that can accurately represent the motivational symptoms of depression in humans. The goal of the present study was to use female and male rats to develop electroencephalography (EEG) markers that can be readily translatable to the pathophysiology of female and male patients with depression. In this study, tetrabenazine (TBZ), a vesicular monoamine transporter-2 (VMAT-2) inhibitor, or a vehicle (VEH) control, was administered to a group of 8 female rats and 7 male rats prior to measuring EEG in the home cage. Recordings were taken from each treatment condition in the medial prefrontal cortex (mPFC), motor (M1/M2), and medial parietal (mParietal) cortices to investigate the effect of TBZ on these cortices and to determine whether they are comparable to the neurological markers associated with depression in humans. It was found that male rats demonstrated a predominant peak frequency at baseline in EEG activity across all three regions in the alpha/theta frequency range (4-12 Hz, with a sharp peak at 6-8.5 Hz frequency range). The sharp 6-8.5 Hz peak was suppressed when TBZ was administered in a 1.0 mg/kg dose. The EEG recordings of the female rats were not significantly affected. These findings can be used as a foundation to develop further EEG studies in behaving rats that can be translated to treatments for clinical depression within humans