Positive allosteric modulation of cannabinoid type-1 receptors: Effects of GAT211 on MK-801-induced behaviors in rats
| dc.contributor.advisor | Howland, John G | |
| dc.contributor.committeeMember | Campanucci, Verónica A | |
| dc.contributor.committeeMember | Bekar, Lane K | |
| dc.contributor.committeeMember | Muir, Gillian D | |
| dc.creator | McElroy, Dan L | |
| dc.creator.orcid | 0000-0002-9797-1676 | |
| dc.date.accessioned | 2020-10-28T17:23:25Z | |
| dc.date.available | 2020-10-28T17:23:25Z | |
| dc.date.created | 2020-09 | |
| dc.date.issued | 2020-10-28 | |
| dc.date.submitted | September 2020 | |
| dc.date.updated | 2020-10-28T17:23:25Z | |
| dc.description.abstract | Antipsychotics 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. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | http://hdl.handle.net/10388/13109 | |
| dc.subject | schizophrenia | |
| dc.subject | antipsychotic | |
| dc.subject | cannabis | |
| dc.subject | THC | |
| dc.subject | NMDA receptor | |
| dc.subject | MK-801 | |
| dc.subject | CB1 receptor | |
| dc.subject | GAT211 | |
| dc.subject | positive allosteric modulation | |
| dc.subject | open field | |
| dc.subject | acoustic startle, prepulse inhibition, locomotor activity | |
| dc.title | Positive allosteric modulation of cannabinoid type-1 receptors: Effects of GAT211 on MK-801-induced behaviors in rats | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Physiology | |
| thesis.degree.discipline | Physiology | |
| thesis.degree.grantor | University of Saskatchewan | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Master of Science (M.Sc.) |