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.