Diazepam-Induced Increases of Synaptic Efficacy in the Hippocampal – Medial Prefrontal Cortex Pathway Are Associated With Its Anxiolytic-like Effect in Rats

Abstract

Abstract. The medial prefrontal cortex (mPFC) has recently been shown to be an important brain region for emotional function as well as cognitive ability. In previous experiments, we studied the population spike amplitude (PSA) in the mPFC induced by stimulation of the CA1/subicular region as an index of synaptic efficacy in the hippocampal-mPFC pathway. In the present study, we investigated the relationship between the anxiolytic effect of diazepam and the changes of synaptic efficacy in this pathway. In contextual fear conditioning tests, diazepam (0.1 mg/kg) was not effective for fear-related freezing behavior. At a dose of 0.5 mg/kg, diazepam decreased freezing behavior 20 min after administration, with no discernible effect 30 min after administration. In electrophysiological experiments, 0.1 mg/kg diazepam had no effect on the PSA in the mPFC. In contrast, 0.5 mg/kg diazepam increased the PSA in the mPFC within 30 min of administration; however, this PSA increase was attenuated over the 30-min period. Based on these results, we propose that the diazepam-induced PSA increase in the mPFC is associated with its anxiolytic-like effect.

The Anxiolytic Potential and Psychotropic Side Effects of an Echinacea Preparation in Laboratory Animals and Healthy Volunteers

“…Although effective doses vary from study to study (e.g. diazepam decreased conditioned fear at doses ranging from 0.5 to 10 mg/kg), conditioned freezing responses are ameliorated but not abolished by anxiolytics, and dose–response curves are usually bell‐shaped (Beck and Fibiger, ; Miyamoto et al ., ; Wislowska‐Stanek et al ., ; Shikanai et al ., ; Haller et al ., ). These and earlier findings (Haller et al ., ) suggest that certain but not all E. angustifolia extracts have anxiolytic effects in laboratory tests at doses that are comparable to those of established anxiolytics.…”