Functional Studies of the 5-HT1A Autoreceptor in Mice

Abstract

The serotonin system, tightly controlled by negative regulation by 5-HT1A autoreceptors, is involved in MDD since manipulating different aspects of the 5-HT systems produces behavioral changes akin to MDD symptoms. Deaf1 knockout mice, which have shown increased 5-HT1A autoreceptor levels, were examined. Conversely, the effect of loss of 5-HT1A autoreceptors in adulthood was studied in 5-HT1AautoKO mice engineered for inducible knockout of the 5-HT1A autoreceptor. Anxiety and depression behavioural assays were performed on the Deaf1KO and 5-HT1AautoKO models. Deaf1KO mice displayed an overall increase in anxious behaviour, yet no change in depressive behaviour relative to controls. Conditional 5-HT1A mice displayed no changes in anxiety or depressive behaviour. Compensation from remaining aspects of the serotonin system and/or other neurological systems may account for some of the behavioural results (or lack thereof). Additional testing that includes a stress paradigm is warranted in order to reveal any stress-dependent vulnerabilities to anxiety and depression.