Cognitive interference as a possible therapeutic strategy to prevent expression of benzodiazepine withdrawal.
Eur J Neurosci
; 50(11): 3843-3854, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31299121
Benzodiazepines are usually prescribed for anxiety and sleep disorders in long-term schedules that may cause drug dependence. Discontinuation after prolonged administration may lead to withdrawal expression, being anxiety the most predominant sign. The context-dependent associative learning process that underlies diazepam dependence can be interfered by pre-exposure to the drug administration context, an effect known as latent inhibition. Considering this background, the primary aim of the present investigation is to develop a therapeutic strategy to prevent diazepam withdrawal in male Wistar rats by interfering with this learning process. Nitric oxide is a crucial player in learning and memory, hippocampal synaptic transmission and in diazepam withdrawal. Then, a secondary goal is to determine how latent inhibition could alter functional plasticity and neuronal nitric oxide synthase enzyme (NOS-1) expression within the hippocampus, by using multi-unitary cell recordings and Western blot, respectively. Our results indicate that chronic diazepam treated animals under latent inhibition did not show anxiety, or changes in hippocampal synaptic transmission, but a significant reduction in NOS-1 expression was observed. Accordingly, pharmacological NOS-1 inhibition resembles behavioral and electrophysiological changes induced by latent inhibition. Contrary, diazepam treated animals under Control protocol expressed anxiety and evidenced an increased hippocampal-plasticity, without alterations in NOS-1 expression. In conclusion, manipulation of the contextual cues presented during diazepam administration may be considered as an effective non-pharmacological tool to prevent the withdrawal syndrome. This behavioral strategy may influence hippocampal synaptic transmission, probably by alterations in nitric oxide signaling pathways in this structure.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Abstinência a Substâncias
/
Ansiolíticos
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Diazepam
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Inibição Psicológica
Tipo de estudo:
Guideline
Limite:
Animals
Idioma:
En
Revista:
Eur J Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Argentina
País de publicação:
França