Differential effects of a chronic treatment with Pregabalin on mature and immature adult hippocampal granule cells

LUCIA COLL; LEMPEL AUGUSTO A; PIRIZ JOAQUIN

Huerta Grande

Congreso; Reunión Anual de la Sociedad Argentina de Neurociencias; 2013

Sociedad Argentina de Neurociencias

Pregabalin (PGB) is an anticonvulsant, analgesic, and anxiolytic drug used inpatients with epilepsy, neuropathic pain, anxiety disorder and migraine. ThoughPGB clinical use is widely extended its physiological mechanism of action is notcompletely understood. PGB targets the α2δ subunit of the voltage dependentcalcium channel shown to be involved in synaptogenesis and adult neurogenesis indentate gyrus a brain area related to some of the pathologies that are currentlytreated with PGB.Animals were cronicaly treated with PGB and the morphological and functionalproperties of adult and new GFP labeled neurons were studied. We found that theapplication of PGB increased the frequency of miniature excitatory post-synapticpotentials, the action potential repolarization amplitude and the AMPA/NMDAratio. All these effects are consistent with the accelerated neuronal development.The degree of maturation of newborn DGCs was determined by measuring theproportion of BrdU cells expressing DCX and Cb. These results are in agreementwith the electrophysiological recordings described above.We found PGB to affect differentially mature and immature DGCs. In immaturegranules cells both electrophysiological and morphological parameters arecompatible with an acceleration of development via PGB. On the other hand, inmature DGCs, PGB seems to decrease glutamatergic transmission excitability andto reduce network activity.