Participação do sistema endocanabinóide em respostas comportamentais induzidas pela inibição do transportador de dopamina

Abstract

Dopamine transpoter (DAT) inhibition induces behavioral changes in animals that can be related to maniac state of Bipolar Disorder (BD) in humans. Due that is an important tool for elucidate the physiopathology of BD. The interactions of dopaminergic and endocannabinoid systemns have been widely studied in attempt to find new therapeutic targets. Endocanabinoid system is compond by CB1 and CB2 receptors, endogenous ligants and enzyms for syntese and degradation of this ligants. In this line, we research how acute (pharmacological) or chronic (genetic) inhibion of DAT is influencied by endocannabinoid system thought administration of agonists, antagonists and two inhibitors of enzyms that degradate endocannabinoid ligants. We analyse this effects in C57Bl6 mice that received an injection of GBR12909, a DAT inhibitor, thereafter. This mice were submitted to locomotors analyses (open field or Behavioral Pattern Monitor – BPM) and Prepulse Inhibiont test (PPI). We also evaluated the effects of CB1 antagonist AM251 in mice with down expression of DAT (DAT KD mice). We observed that 3 mg/Kg dose of AM251 was able to prevent as the increase of locomotion induced by GBR12909 as what exibided by DAT KD mice. Interesantly the administration of THC also prevent the increase of locomotion induced by GBR12909. We conclude that CB1 receptor participate of DAT inhibition induced responses and can be a possible pharmacological target for new anti-maniac drugs.