IFEC   20925
INSTITUTO DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Contextual cues relevance in the expression of diazepam withdrawal: correlation to hippocampal synaptic plasticity and hippocampal Arc protein expression.
Autor/es:
CAROLINA MONTI; LAURA GABACH; MARIELA F. PEREZ; OSCAR A. RAMÍREZ
Lugar:
San Diego, California
Reunión:
Congreso; Society for Neuroscience; 2010
Institución organizadora:
Society for Neuroscience
Resumen:
Contextual cues linked to drug experience have been frequently associated to craving and relapse, with this phenomenon being described in humans and experimental animals. Hippocampal synaptic plasticity has been related to learning and adaptive processes developed during chronic drug administration, leading many authors to suggest the existence of a common neurobiological mechanism mediating drug addiction and memory. We have demonstrated that the environmental context associated to withdrawal experience was able to evoke the same behavioral alteration observed after chronic benzodiazepine administration to rats. Furthermore, we have found an increased hippocampal synaptic plasticity and hippocampal Activity-regulated cytoskeletal-associated protein (Arc) protein expression, as a sensitive marker of neuronal activity critically involved in the storage of contextual memory, during withdrawal and after re-exposure to the context associated with anxiety expression, a characteristic sign of benzodiazepines withdrawal. Recently it has been shown that Protein Kinase M Zeta (PKMZ) is critical for the maintenace of hippocampal long-term Potentiation (LTP) and spatial, instrumental, and classically conditioned long-term memories. Also, a link between Arc, PKMZ and LTP has been proposed. Considering all these facts, the major challenge of this work is to find out whether the retrieval of the same behavioral alteration observed during Diazepam withdrawal, evoked by the contextual cues linked to the withdrawal experience and the associated increment on hippocampal synaptic plasticity, could be affected by the administration of a PKMZ ihibitor or by changes in the contextual cues related to drug experience. Our results indicate that alterations in the contextual cues during the re-exposure to the context associated with anxiety expression on day 15 of withdrawal prevented the retrieval of the drug experience memory. Studies are underway to determine whether the hippocampal synaptic plasticity is also affected by changes in contextual cues or by the administration of PKMZ inhibitor. These results will help us to demonstrate the participation of hippocampus in the temporary maintenance of this memory trace during benzodiazepines withdrawal.