Friemel Chris M, Zimmer Andreas, Schneider Miriam
Reseach Group Developmental Neuropsychopharmacology, Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.
Neuropsychopharmacology. 2014 Sep;39(10):2387-96. doi: 10.1038/npp.2014.86. Epub 2014 Apr 10.
The endocannabinoid (ECB) system has emerged recently as a key mediator for reward processing. It is well known that cannabinoids affect appetitive learning processes and can induce reinforcing and rewarding effects. However, the involvement of the ECB system in hedonic aspects of reward-related behavior is not completely understood. With the present study, we investigated the modulatory role of the ECB system on hedonic perception, measured by the pleasure attenuated startle (PAS) paradigm for a palatable food reward. Here, a conditioned odor is thought to induce a pleasant affective state that attenuates an aversive reflex-the acoustic startle response. Modulatory effects of the CB1 receptor antagonist/inverse agonist SR1411716 and the cannabinoid agonist WIN 55 212-2 on PAS were examined in rats. PAS was also measured in CB1 receptor knockout (KO) and wild-type (WT) mice. Pharmacological inhibition as well as the absence of CB1 receptors was found to reduce PAS, whereas WIN 55 212-2 administration increased PAS. Finally, presentation of a conditioned reward cue was found to induce striatal FosB/ΔFosB expression in WT mice, but not in KO mice, indicating a reduced stimulation of reward-related brain regions in conditioned KO mice by odor presentation. We here show that in addition to our previous studies in rats, PAS may also serve as a valuable and suitable measure to assess hedonic processing in mice. Our data further indicate that the ECB system, and in particular CB1 receptor signaling, appears to be highly important for the mediation of hedonic aspects of reward processing.
内源性大麻素（ECB）系统最近已成为奖赏处理的关键调节因子。众所周知，大麻素会影响食欲学习过程，并能诱导强化和奖赏效应。然而，ECB系统在与奖赏相关行为的享乐方面的作用尚未完全明确。在本研究中，我们通过美味食物奖赏的愉悦减弱惊吓（PAS）范式，研究了ECB系统对享乐感知的调节作用。在此，一种条件性气味被认为会诱导一种愉悦的情感状态，从而减弱一种厌恶反射——听觉惊吓反应。在大鼠中检测了CB1受体拮抗剂/反向激动剂SR1411716和大麻素激动剂WIN 55 212-2对PAS的调节作用。还在CB1受体基因敲除（KO）小鼠和野生型（WT）小鼠中测量了PAS。发现药理学抑制以及CB1受体缺失均可降低PAS，而给予WIN 55 212-2则可增加PAS。最后，发现呈现条件性奖赏线索可诱导野生型小鼠纹状体FosB/ΔFosB表达，但在基因敲除小鼠中则不然，这表明在条件性基因敲除小鼠中，气味呈现对奖赏相关脑区的刺激减弱。我们在此表明，除了我们之前在大鼠中的研究外，PAS也可作为评估小鼠享乐处理的一种有价值且合适的指标。我们的数据进一步表明，ECB系统，尤其是CB1受体信号传导，似乎对奖赏处理的享乐方面的调节非常重要。
