SIGMA RECEPTOR AGONISTS SHOW ANTIDEPRESSANT‐LIKE EFFECTS IN MICE

Abstract

Many antidepressant drugs interact with sigma (σ) receptors and their activation produces antidepressant-like effects. σreceptors are localized in brain regions that are affected in depression. Therefore, σreceptor agonists were evaluated for antidepressant-like activity in mice using the forced swim test. Mice were injected (i.p.) with a drug or control, and then placed in a cylinder of water. Immobility time was quantified, and reduction in immobility time was used as an indicator of antidepressant-like actions. Desipramine and fluvoxamine, clinically used antidepressants, served as positive controls and were shown to dose-dependently reduce immobility time. The well studied σ receptor agonist di-o-tolylguanidine also reduced immobility time. Likewise, the novel σreceptor agonists UMB23, UMB41, and UMB82 produced antidepressant-like actions by reducing immobility time (P<0.01). Locomotor activity was measured to determine whether stimulant effects could account for apparent antidepressant-like actions in forced swim tests. After the administration of drugs, mice were put into chambers with photocell monitors. Locomotor activity was quantified by continuous automated counting of photobeam interruptions. Data were evaluated corresponding to the data collection period of forced swim tests. This part of the study showed that changes in locomotor activity could not explain the antidepressant-like actions of the σ receptor agonists in forced swim tests. Together, the data provide further evidence that σ receptor agonists represent a possible new class of antidepressant medication.