RationaleOlfactory bulbectomy (OBX) in a laboratory rodent leads to numerous behavioral deficits and involves cognitive and motor changes that are used to model major depression, but may also be a valuable tool in the study of neurodegenerative disorders like Alzheimer’s disease.ObjectivesThis experiment evaluated the effects of simvastatin, a cholesterol-lowering drug with putative neuroprotective properties, on OBX-induced behavioral changes.ResultsChronic administration of simvastatin, starting 48 h after surgery, did not have any behavioral effect in OBX rats, as tested in open field, passive avoidance and object-recognition paradigms. In control rats, simvastatin treatment resulted in an improved performance in both the passive avoidance and the object-in-place task.ConclusionIn the present study, simvastatin treatment enhanced cognition in intact rats, but had no effect in OBX rats. These results are in line with the idea that statins may attenuate (early) age-associated cognitive decline in humans.

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The inability of CRF₁ receptor antagonists to block pharmacological disruption of sensorimotor gating suggests that the involvement of CRF₁ receptors in the modulation of dopaminergic and glutamatergic neurotransmission relevant for sensory gating is limited. Furthermore, the alterations observed in CRFtg mice support the notion that long-term elevated central CRF levels induce changes in these neurotransmitter systems.