Protective effect of cannabinoid CB1 receptor activation against altered intrinsic repetitive firing properties induced by Aβ neurotoxicity

The amyloid beta (A beta) protein is believed to be the key pathological mediator of Alzheimer's disease (AD) which is the first and most well known type of dementia. Despite a growing body of evidence indicating that A beta neurotoxicity induces changes in synaptic function, little effort, if any, has been made to investigate the effect of in vivo A beta treatment on intrinsic neuronal properties. The present study was designed to examine the effects that in vivo A beta treatment have on the intrinsic repetitive firing properties of CA1 pyramidal neurons, using whole cell patch clamp recording. Protective effect of cannabinoid CB1 receptor activation was also investigated against A beta-induced alterations in evoked electrophysiological activities. The findings from present study demonstrated that a bilateral injection of A beta into the prefrontal cortex causes robust changes in activity-dependent electrophysiological responses in hippocampal CA1 pyramidal neurons. The effects of A beta treatment alone was almost completely prevented by combined treatment with A beta and ACEA, a selective CBI receptor agonist. It can be concluded A beta treatment reduces evoked neuronal activity and activation of CB1 cannabinoid receptors may have beneficial preventative effects on A beta-induced electrophysiological changes. (C) 2011 Elsevier Ireland Ltd. All rights reserved.