Foraging in rodents is highly sensitive to pharmacological disruptions
Location
D.P. Culp Center Ballroom
Start Date
4-5-2024 9:00 AM
End Date
4-5-2024 11:30 AM
Poster Number
66
Name of Project's Faculty Sponsor
Sivarao Digavalli
Faculty Sponsor's Department
Pharmaceutical Sciences
Competition Type
Competitive
Type
Poster Presentation
Presentation Category
Health
Abstract or Artist's Statement
Schizophrenia is a serious mental illness which affects many aspects of a patient’s life. The psychosocial deficits in schizophrenia patients can be attributed to impaired executive function, though the illness itself is still not fully understood. Animal models of schizophrenia play an important role in research to gain a better understanding of the disease state and test new treatments. MK801, a potent blocker of NMDA receptors, has been used in rodents to induce schizophrenic-like behaviors such as hyperactivity and cognitive deficits, including executive functioning. In rodents, foraging for food is an essential task for survival; foraging is made up of many smaller tasks that rely on planning, decision making, problem-solving, and working memory. We tested the effects of MK801 on the foraging efficiency of rats. In this experiment, overnight fasted Sprague-Dawley rats (N=12) were injected with either saline (sc), 0.025 mg/kg MK801, or 0.05 mg/kg MK801, 30 minutes prior. Foraging efficiency was measured by the time taken to find all 5 treats in a puzzle toy that hides the treats in many recessed locations. MK801 at 0.05 mg/kg was found to significantly increase foraging time, relative to vehicle (P=0.0009; Friedman one-way ANOVA). Moreover, motor activity was significantly higher in this group relative to vehicle (P=0.0009). No difference was noted between vehicle treatment and the low dose of MK801 (P>0.05) for foraging or motor activity. These data suggest that MK801 impairs foraging abilities in rodents, increases locomotor activity, and impacts cognitive performance. In a follow up experiment, we tested the ability of clozapine (Clz), an antipsychotic agent, to reverse the effects of MK801 shown in the first experiment. SD rats (N=12) were dosed in a double-dummy style using injections of saline, 0.05 mg/kg MK801, or 5 mg/kg clozapine 30 minutes prior to foraging. Veh/MK801 showed a trend level increase in foraging time (P=0.08), relative to Veh/Veh. However, Veh+Clz markedly increased the foraging time, relative to Veh/Veh and was no different from Clz/MK801 treatment. Interestingly, locomotor activity was high in Veh/MK801 group but was low in all other groups. Based on these data, we concluded that MK801 disrupts foraging and increases locomotor activity. However, clozapine by itself markedly impaired foraging and severely curtailed locomotor activity, perhaps by making the rats drowsy, an effect seen in the clinic as well. Because of this confounding effect of clozapine, we couldn’t evaluate foraging performance in Clz/MK801 group.
Foraging in rodents is highly sensitive to pharmacological disruptions
D.P. Culp Center Ballroom
Schizophrenia is a serious mental illness which affects many aspects of a patient’s life. The psychosocial deficits in schizophrenia patients can be attributed to impaired executive function, though the illness itself is still not fully understood. Animal models of schizophrenia play an important role in research to gain a better understanding of the disease state and test new treatments. MK801, a potent blocker of NMDA receptors, has been used in rodents to induce schizophrenic-like behaviors such as hyperactivity and cognitive deficits, including executive functioning. In rodents, foraging for food is an essential task for survival; foraging is made up of many smaller tasks that rely on planning, decision making, problem-solving, and working memory. We tested the effects of MK801 on the foraging efficiency of rats. In this experiment, overnight fasted Sprague-Dawley rats (N=12) were injected with either saline (sc), 0.025 mg/kg MK801, or 0.05 mg/kg MK801, 30 minutes prior. Foraging efficiency was measured by the time taken to find all 5 treats in a puzzle toy that hides the treats in many recessed locations. MK801 at 0.05 mg/kg was found to significantly increase foraging time, relative to vehicle (P=0.0009; Friedman one-way ANOVA). Moreover, motor activity was significantly higher in this group relative to vehicle (P=0.0009). No difference was noted between vehicle treatment and the low dose of MK801 (P>0.05) for foraging or motor activity. These data suggest that MK801 impairs foraging abilities in rodents, increases locomotor activity, and impacts cognitive performance. In a follow up experiment, we tested the ability of clozapine (Clz), an antipsychotic agent, to reverse the effects of MK801 shown in the first experiment. SD rats (N=12) were dosed in a double-dummy style using injections of saline, 0.05 mg/kg MK801, or 5 mg/kg clozapine 30 minutes prior to foraging. Veh/MK801 showed a trend level increase in foraging time (P=0.08), relative to Veh/Veh. However, Veh+Clz markedly increased the foraging time, relative to Veh/Veh and was no different from Clz/MK801 treatment. Interestingly, locomotor activity was high in Veh/MK801 group but was low in all other groups. Based on these data, we concluded that MK801 disrupts foraging and increases locomotor activity. However, clozapine by itself markedly impaired foraging and severely curtailed locomotor activity, perhaps by making the rats drowsy, an effect seen in the clinic as well. Because of this confounding effect of clozapine, we couldn’t evaluate foraging performance in Clz/MK801 group.