Negative allosteric modulation of alpha 5-containing GABA A receptors engenders antidepressant-like effects and selectively prevents age-associated hyperactivity in tau-depositing mice

Rationale Associated with frank neuropathology, patients with Alzheimer’s disease suffer from a host of neuropsychiatric symptoms that include depression, apathy, agitation, and aggression. Negative allosteric modulators (NAMs) of α5-containing GABAA receptors have been suggested to be a novel target for antidepressant action. We hypothesized that pharmacological modulation of this target would engender increased motivation in stressful environments.