Psychology
Document Type
Poster Presentation
Location
Indianapolis, IN
Subject Area
Psychology
Start Date
11-4-2014 12:00 PM
End Date
11-4-2014 12:59 PM
Sponsor
Christopher Lapish (Indiana University/Purdue University at Indianapolis)
Description
Schizophrenia (SZ) is a chronic mental disorder affecting approximately 1% of the world's population, and is characterized by positive and negative symptoms both of which impair normal functioning. While a number of treatment options exist for positive symptoms, there are virtually none for the negative and cognitive symptoms. Hindering the development of treatments for these symptoms is a lack of translational biomarkers that can be applied across species. Identifying translational biomarkers could significantly improve our understanding of the etiology of SZ and aid in drug development. Therefore, we validated measures of cognitive performance similar to those observed in patients with SZ using a "two-hit" rodent model, and then assessed the effectiveness of N-Acetyl-Cysteine (NAC) as a novel drug treatment to remediate impairments seen in cognitive function. In this experiment, male pups of Sprague Dawley dams were used. Pups from each litter were split into two groups: maternally deprived (MD) or sham. On PD 9, pups from the MD group (n= 9) were weighed and removed from their mothers for 24 hours. MD acts as an early life stressor and is believed to be associated with the development of SZ, and therefore was used as the first model to induce SZ. Pups from the sham group (n= 9) served as controls. On PD 75-88, MD rats (n= 9) received an intraperitoneal injection of NAC (90.0 mg/kg; n= 5) or saline (n= 4). All sham rats received saline. Two days after drug treatment, all rats received an acute injection of 2.0 mg/kg of Phencyclidine (PCP), an NMDA antagonist, used to induce SZ like symptoms in rats by altering glutamatergic signaling. The day after injection, temporal memory and recognition memory were assessed using temporal order recognition (TOR) and novel object recognition (NOR) tasks. Rats were also assessed on these two tasks after chronic treatment of PCP (2.0 mg/kg for 6 days), to examine the effect of further alterations in glutamatergic signaling on cognitive function. Very preliminary results indicate that there are no detectable differences in TOR and NOR between the MD group that received NAC compared to the MD group that received saline, as well as no significant differences between the MD and Sham groups that received saline. Furthermore, there were no differences between any of the groups after chronic PCP administration. At this time the group sizes are small and prevent us from reaching a conclusion, but the available data suggests that NAC treatment does not improve temporal or recognition memory in this rodent model of SZ. Additional animals are being tested to increase group sizes and to have larger power when running the analyses.
Evaluating Differences in Cognitive Function After N-Acetyl-Cysteine Treatment in a Two-Hit Rat Model of Schizophrenia
Indianapolis, IN
Schizophrenia (SZ) is a chronic mental disorder affecting approximately 1% of the world's population, and is characterized by positive and negative symptoms both of which impair normal functioning. While a number of treatment options exist for positive symptoms, there are virtually none for the negative and cognitive symptoms. Hindering the development of treatments for these symptoms is a lack of translational biomarkers that can be applied across species. Identifying translational biomarkers could significantly improve our understanding of the etiology of SZ and aid in drug development. Therefore, we validated measures of cognitive performance similar to those observed in patients with SZ using a "two-hit" rodent model, and then assessed the effectiveness of N-Acetyl-Cysteine (NAC) as a novel drug treatment to remediate impairments seen in cognitive function. In this experiment, male pups of Sprague Dawley dams were used. Pups from each litter were split into two groups: maternally deprived (MD) or sham. On PD 9, pups from the MD group (n= 9) were weighed and removed from their mothers for 24 hours. MD acts as an early life stressor and is believed to be associated with the development of SZ, and therefore was used as the first model to induce SZ. Pups from the sham group (n= 9) served as controls. On PD 75-88, MD rats (n= 9) received an intraperitoneal injection of NAC (90.0 mg/kg; n= 5) or saline (n= 4). All sham rats received saline. Two days after drug treatment, all rats received an acute injection of 2.0 mg/kg of Phencyclidine (PCP), an NMDA antagonist, used to induce SZ like symptoms in rats by altering glutamatergic signaling. The day after injection, temporal memory and recognition memory were assessed using temporal order recognition (TOR) and novel object recognition (NOR) tasks. Rats were also assessed on these two tasks after chronic treatment of PCP (2.0 mg/kg for 6 days), to examine the effect of further alterations in glutamatergic signaling on cognitive function. Very preliminary results indicate that there are no detectable differences in TOR and NOR between the MD group that received NAC compared to the MD group that received saline, as well as no significant differences between the MD and Sham groups that received saline. Furthermore, there were no differences between any of the groups after chronic PCP administration. At this time the group sizes are small and prevent us from reaching a conclusion, but the available data suggests that NAC treatment does not improve temporal or recognition memory in this rodent model of SZ. Additional animals are being tested to increase group sizes and to have larger power when running the analyses.