Participation of dorsal raphe nucleus in the behavioral alteration observed after discontinuation of chronic diazepam administration: possible neural circuitry involved.
Previous findings from our laboratory have demonstrated a positive correlation between the development of tolerance to diazepam (DZ) 5 mg/kg/day over 4 days, and increased hippocampal synaptic plasticity. It seems likely that a similar plastic phenomenon may occur on hippocampal formation after chronic (18 days) DZ administration. We postulate hippocampal long-term potentiation (LTP) underlying substrate to the behavioral alteration observed after chronic DZ administration. In the present study, we investigated the involvement of the serotonergic (5-HT) system in the possible neural circuitry recruited during DZ withdrawal and in the increased hippocampal synaptic plasticity associated with the discontinuation of chronic DZ administration. The results of the current research demonstrate an increased neuronal activity in the dorsal raphe nucleus (DRN) during withdrawal. Previous MK-801 administration impairs the development of anxiety signs observed during withdrawal and the concomitant increased electrical activity on 5-HT neurons on DRN. These results are discussed in terms of the participation of 5-HT system in the modulation of hippocampal plasticity developed on DZ withdrawal.
Almirón
Romina Soledad
RS
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Ramírez
Oscar Angel
OA
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D003975:Diazepam / Q000008:administration & dosage* / Q000009:adverse effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004594:Electrophysiology / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009415:Nerve Net / Q000502:physiology*; D011903:Raphe Nuclei / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D012701:Serotonin; D016291:Dizocilpine Maleate; D003975:Diazepam