Cannabinoid receptor type 1 (CB₁R) is widely distributed in the substantia nigra pars reticulata (SNpr). However, the role of CB₁R at the SNpr level in threatening situations is poorly understood. We investigated the role of CB₁R in the SNpr on the expression of fear responses in mice confronted with urutu-cruzeiro pit vipers. First, a bidirectional neurotracer was injected into the SNpr; then, immunostaining of the vesicular GABA transporter was conducted at the levels of the striatum (CPu) and deep layers of the superior colliculus (dlSC). In addition, CB₁R immunostaining and GABA labelling were performed in the SNpr. Using a prey-versus-snake paradigm, mice were pretreated with the CB₁R antagonist AM251 (100 pmol) and treated with the endocannabinoid anandamide (AEA, 5 pmol) in the SNpr, followed by bicuculline (40 ng) in the dlSC, and were then confronted with a snake. Bidirectional neurotracers associated with immunofluorescence showed the GABAergic striatonigral and nigrotectal pathways. Furthermore, we showed that CB₁R labelling was restricted to axonal fibres surrounding SNpr GABAergic cells. We also demonstrated a decrease in the defensive behaviours of mice treated with AEA in the SNpr, but this effect was blocked by co-treatment with AM251 in this structure. Taken together, our results show that the panicolytic consequences of the AEA enhancement in the SNpr are signalled by CB₁R, suggesting that CB₁R localised in axon terminals of CPu GABAergic neurons in the SNpr modulates the activity of the nigrotectal GABAergic pathway during the expression of defensive behaviours in threatening situations.

大麻素受体 1 型 (CB ₁ R) 广泛分布于黑质网状部 (SNpr)。然而，人们对 CB ₁ R 在 SNpr 级别在威胁情况下的作用知之甚少。我们研究了 CB ₁ R 在 SNpr 中对面对urutu-cruzeiro pit vipers 的小鼠的恐惧反应表达的作用。首先，将双向神经示踪剂注入 SNpr；然后，在纹状体 (CPu) 和上丘深层 (dlSC) 的水平上进行囊泡 GABA 转运蛋白的免疫染色。此外，在 SNpr 中进行了CB ₁ R 免疫染色和 GABA 标记。使用猎物对蛇的范式，用 CB ₁预处理小鼠R 拮抗剂 AM251（100 pmol）并在 SNpr 中用内源性大麻素 anandamide（AEA，5 pmol）处理，然后在 dlSC 中用荷包牡丹碱（40 ng）处理，然后与蛇对峙。与免疫荧光相关的双向神经示踪剂显示 GABA 能纹状体黑质和 nigrotectal 通路。此外，我们表明 CB ₁ R 标记仅限于围绕 SNpr GABAergic 细胞的轴突纤维。我们还证明了在 SNpr 中用 AEA 处理的小鼠的防御行为有所减少，但这种效果被这种结构中的 AM251 共同处理所阻止。总之，我们的结果表明 SNpr 中 AEA 增强的恐慌后果由 CB ₁ R发出信号，表明 CB ₁位于 SNpr 中 CPu GABA 能神经元的轴突末端的 R 在威胁情况下防御行为的表达过程中调节 nigrotectal GABA 通路的活动。