title: Hippocampus and locus coeruleus activity on rats chronically treated with diazepam.
abstract: The neural mechanisms underlying benzodiazepine (BZD) dependence remain equivocal. The present studies tested the hypothesis that similar neural circuitry 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 synaptic plasticity in slices from rats chronically treated with DZ (5 mg/kg/18 days), assessed as a decrease of the threshold in the stimulation rate for long-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 activity of locus coeruleus (LC) norepinephrine (NE) neurons in rats tested 24 h after the last DZ injection showed a significant increase. On the other hand, rats that after chronic DZ administration did not develop signs of withdrawal and exhibited a similar pattern of discharge on LC-NE nucleus compared 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 alterations accompanying chronic DZ administration and withdrawal.
authors.affiliation: Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina.
authors.forename: M F
authors.initials: MF
authors.lastname: Pérez
authors.forename: F J
authors.initials: FJ
authors.lastname: Nasif
authors.forename: G R
authors.initials: GR
authors.lastname: Marchesini
authors.forename: L E
authors.initials: LE
authors.lastname: Maglio
authors.forename: O A
authors.initials: OA
authors.lastname: Ramirez
mesh_terms: D000818:Animals; D003975:Diazepam / Q000008:administration & dosage*; D018757:GABA Modulators / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018757:GABA Modulators; D003975:Diazepam