Enkephalinergic system is involved in cocaine induced behavioral sensitization and the associated increase in brain derived neurotrophic factor in nucleus accumbens

AVALOS MP; MONGI BRAGATO B; ZAMPONI E; MASCO DANIEL; CANCELA LILIANA

Córdoba

Congreso; XIV Reunión Nacional - III Encuentro Internacional Asociación Argentina de Ciencias del Comportamiento; 2013

Repeated intermittentexposure to cocaine produces a progressively greater locomotor response to thedrug (behavioral sensitization) which is generally coupled to a progressivelygreater drug-induced increases in dopamine efflux in the nucleus accumbens (NAc). The process underlying behavioralsensitization involves a complex interplay between dopamine (DA) and othersneurotransmitters and neuropeptides such as glutamate, opioid peptides and brain-derivedneurotrophic factor growth (BDNF). BDNF regulate drug-inducedlong-term neuroadaptations that encompass alterations in molecular componentsat the synapse and changes in gene expression. BDNF protein and its receptor (TrkB) are induced in the Prefrontalcortex (Pfc), NAc and Ventral Tegmental Area (VTA) after chronic cocainetreatment. BDNF is reported to alter glutamatergic and dopaminergictransmission in the brain areas associated with cocaine-induced sensitization. Onthe other hand, opioid receptors and endogenous opioid peptides,mainly enkephalin, are largely distributed in the mesocorticolimbic system. There is pharmacological evidence for a roleof opioid receptors in the developmentand expression of psychostimulantinduced sensitization.  However, enkephalin contribution to the inductionand expression of this phenomenon on behavioral and associated molecularparameters has been poorly studied. The main goal of thisstudy was to demonstrate the involvement of the enkephalinergic system incocaine-induced behavioral sensitization, and their association with changesin BDNF and its receptor. Male C57B/6J wild type (WT) and preproenkephalinknockout (KO Penk) mice were daily treated with cocaine (15mg/Kg i.p.) andvehicle for 9 days. On day 21 of the treatment the following experiments were done:1) Immunofluorescence: BDNF and TrkB levels were determined in PfC, NAc, DorsalStriatum and VTA in response to saline and cocaine challenge. 2) Western blot:to determinate pTrkB levels in these brain areas.  We found that chroniccocaine administration increases BDNF and pTrkB levels in NAc and VTA comparedto controls animals. These effects are absent in KO mice Penk (-/-).Theseresults demonstrate that enkephalinergic system is involved in cocaine- inducedalterations in neurotrophic factors in the NAc and indicate that preproenkephalin-derived opioid peptides are strongly involved in the long-term plastic changes underlying behavioralsensitization to cocaine.