COGNITIVE INTERFERENCE AS A POSSIBLE THERAPEUTIC STRATEGY TO PREVENT EXPRESSION OF BENZODIAZEPINE WITHDRAWAL

EMILCE ARTUR DE LA VILLARMOIS; MARIELA F. PÉREZ.

EUROPEAN JOURNAL OF NEUROSCIENCE

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2019

0953-816X

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.