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

MONGI BRAGATO, B; AVALOS, M.P.; ZAMPONI, E.; MASCO, D.; CANCELA, L.M.

Workshop; Congreso de la Sociedad Argentina de Investigación en Neurociencias; 2013

Enkephalinergic system is involved in cocaine-induced behavioral sensitization and the associated increase in brain-derived neurotrophic factor in nucleus accumbens.Repeated intermittent exposure to cocaine produces a progressively greater locomotor response to the drug (behavioral sensitization) which is generally coupled to a progressively greater drug-inducedincreases in dopamine efflux in the nucleus accumbens (NAc). The process underlying behavioral sensitization involves a complex interplay between dopamine (DA) and others neurotransmitters andneuropeptides such as glutamate, opioid peptides and brain-derived neurotrophic factor (BDNF). BDNF regulate drug-induced long-term neuroadaptations that encompass alterations in molecularcomponents at the synapse and changes in gene expression and is reported to alter glutamatergic and dopaminergic transmission in the brain areas associated with cocaine-induced sensitization. BDNFprotein and its receptor (TrkB) are induced in the Prefrontal cortex (PFC), NAc and Ventral Tegmental Area (VTA) after chronic cocaine treatment. On the other hand, opioid receptors and endogenousopioid peptides, mainly enkephalin, are largely distributed in the mesocorticolimbic system. There is pharmacological evidence for a role of opioid receptors in the development and expression ofpsychostimulant induced sensitization. However, enkephalin contribution to the induction and expression of this phenomenon on behavioral sensitization and associated molecular parameters has beenpoorly studied. The main goal of this study was to demonstrate the involvement of the enkephalinergic system in cocaine-induced behavioral sensitization, and their association with changes in BDNF andits receptors.