CB1R mediates oleamide's reward while 5HT2cR mediates aversion in the nucleus accumbens shell of rats

摘要

In this study, we have pursued to assess oleamide's potential role in reward and aversion mechanisms. To reach this goal we infused oleamide, either 1 mu g into the nucleus accumbens shell (NAccS) and evaluated its effects on conditioned place preference (CCP) or 10 mu g, to evaluate conditioned place aversion (CPA). Extinction and reinstatement were also evaluated in both cases. We sought to determine if CPP occurs via cannabinoid receptor 1 (CB1R) and CPA via serontoninergic 2c receptor (5HT2cR). Results revealed that 1 mu g of oleamide administered bilaterally into the NAccS induced CPP, while 10 mu g induced CPA. In both conditions CPP or CPA, reinstatement after extinction was induced. AM251 (CB1R inverse-agonist) prevented CPP induced with 1 mu g; while SB242084 (5HT2cR antagonist) not only prevented CPA induced with 10 mu g but caused a switch to CPP. These results suggest that oleamide at low doses promotes reward through CB1R, and aversion at high doses via 5HT2cR.