Hippocampus and locus coeruleus activity on rats chronically treated with diazepam

The neural mechanisms underlying benzodiazepine (BZD) dependence remain equ ivocal. The present studies tested the hypothesis that similar neural circu itry might be involved in the effects of chronic 7-chloro-1-methyl-5-phenyl -3H-1,4-benzodiazepine-2(1H)-one, diazepam (DZ, Roche), administration and withdrawal. The results of our study showed an increased hippocampal synapt ic plasticity in slices from rats chronically treated with DZ (5 mg/kg/18 d ays), assessed as a decrease of the threshold in the stimulation rate for l ong-term potentiation (LTP) elicitation. Rats with the same schedule of DZ administration but without signs of withdrawal behaved similarly to vehicle -treated ones (VEH), in the threshold to induce LTP. Furthermore, the activ ity of locus coeruleus (LC) norepinephrine (NE) neurons in rats tested 24 h after the last DZ injection showed a significant increase. On the other ha nd, rats that after chronic DZ administration did not develop signs of with drawal and exhibited a similar pattern of discharge on LC-NE nucleus compar ed with their controls. We conclude that chronic DZ administration enhances both hippocampal. synaptic plasticity and activity of LC-NE neurons. This neural system could be the biological substrate underlying the behavioral a lterations accompanying chronic DZ administration and withdrawal. (C) 2001 Elsevier Science Inc. All rights reserved.