| dc.description.abstract | Bipolar disorder (BD) is a prevalent psychiatric disorder affecting about 1% of the world’s population. However, there is still a lack of adequate treatment for BD. Mania state, the defining feature of BD, manifests insomnia, aggression, and motor hyperactivity, possibly due to dysregulation of the dopaminergic system. In BD lower dopamine transporter (DAT) expression and function are observed which leads to decreased dopamine metabolism which may cause elevated dopamine transmission during mania state.
Cannabis is used in higher rates in people with BD than in the general population. THC, a psychoactive compound present in cannabis, decreases dopamine levels over time, and therefore, with the elevated dopamine levels observed in bipolar mania, may be able to treat the mania-like symptoms of BD.
DAT knockdown (KD) mice reconstruct BD-related behaviors such as hyperexploratory and risky decision- making behavior in the behavioral pattern monitor (BPM) and may be useful to develop newer treatment strategies for BD mania. We investigated if hyperexploratory behavior of DAT KD mice would decrease after chronically administering THC (14 days) in the behavioral pattern monitor (BPM). 45 mice (51% DAT KD, 22% female) were intraperitoneal injected of either THC (3mg/kg) or saline for 14 consecutive days and then tested in the BPM.
Another cohort of DAT KD mice in the BPM, other cohort DAT KD mice were tested in the temporal discrimination task (TDT). The TDT measures temporal perception which altered in BD and by THC. Therefore, we used the TDT to investigate the effect of THC on temporal perception of these subjects. The data we provide is data from during the training phase. 45 mice (54% DAT KD, 56% female) were trained in the TDT task, with each session duration being 30 minutes.
The 19 sessions were insufficient for all mice to attain criterion in the TDT (> 85% correct), although current training revealed no sex or genotype differences in training to-date. Chronic THC treatment attenuated exploratory behavior in DAT KD mouse model of bipolar mania, with a trend effect (p = 0.055) in rearing, and a similar effect in holepoking.
Chronic THC treatment on DAT KD genotype might attenuate exploratory behavior in DAT KD model of bipolar mania. Moreover, when mice perform the TDT task consistently investigation on the effect of chronic THC treatment on temporal perception will be performed. | |
