Howland, John G2020-10-282020-10-282020-092020-10-28Septemberhttp://hdl.handle.net/10388/13109Antipsychotics help alleviate the positive symptoms associated with schizophrenia; however, their debilitating side effects spur the search for better treatment options. Acute N-methyl-D-aspartate receptor (NMDAR) blockade with noncompetitive antagonists such as MK-801 has been used to screen novel compounds for their antipsychotic potential in rodent models. Given interactions between NMDAR and cannabinoid type 1 receptors (CB1R), we tested the ability of GAT211, a CB1R positive allosteric modulator, to reverse two behavioural effects of acute MK-801 treatment, including: (1) increased locomotor activity; and (2) reduced prepulse inhibition (PPI) of the acoustic startle response. Male, Long Evans rats were treated with MK-801 (0.15 mg/kg) and/or GAT211 (0.3-3.0 mg/kg) and locomotor activity or PPI were assessed 15 min later. As expected, acute MK-801 produced a profound increase in locomotor activity and impaired PPI. GAT211 treatment alone dose-dependently reduced locomotor activity and the acoustic startle response. GAT211 (3.0 mg/kg) also blocked the exaggerated locomotor activity caused by MK-801 and showed some modest ability to normalize MK-801-induced PPI impairments. These findings support continued preclinical research regarding the usefulness of CB1R positive allosteric modulators as novel antipsychotic medications.application/pdfschizophreniaantipsychoticcannabisTHCNMDA receptorMK-801CB1 receptorGAT211positive allosteric modulationopen fieldacoustic startle, prepulse inhibition, locomotor activityThesis2020-10-28