Changes in hippocampal Arc protein expression and synaptic plasticity by the presentation of contextual cues linked to drug experience

Abstract

Contextual cues linked to drug experience have been frequently associated to craving and relapse, with this phenomenon being described in human and experimental animals. Hippocampal synaptic plasticity has been related to learning, memory, and adaptive processes developed during chronic administration of drug abuse. In this study, we investigated if the environmental context associated with withdrawal experience was able to evoke the same behavioral alteration observed after chronic benzodiazepine administration. Furthermore, we studied the hippocampal synaptic plasticity and anatomical expression of Arc protein during withdrawal and the re-exposure to the context associated with anxiety expression (characteristic sign of benzodiazepines withdrawal). It was demonstrated that re-exposure evoked on days 15 and 25 after the first exposure the same behavior. An increased hippocampal synaptic plasticity, expressed as a lower threshold to induce long-term potentiation on dentate gyrus, was observed in animals dependent on diazepam and during retrieval, in the same group, until day 15. This plastic change disappeared 25 days after the first exposure. An overexpression of Arc protein in the dorsal dentate gyrus and CA1 on the first day of withdrawal in the dependent animals was observed.