Acute stress induces different changes on the expression of CB1 receptors in the hippocampus of two lines of male rats differing in their response to stressors

The stress-induced alterations in cognitive processes and psychiatric disorders can be accelerated when acute stressors challenge the hippocampal functions. To address this issue, we used Western Blot (WB) and immunohistochemistry assays to investigate the impact of acute forced swimming (FS) on the expression of the CB1 cannabinoid receptors (CB1R) in the hippocampus (HC) of the male outbred Roman High- (RHA) and Low-Avoidance (RLA) rat lines, one of the most validated genetic models for the study of behavior related to fear/anxiety and stress-induced depression. The distinct responses to FS confirmed the different behavioral strategies displayed by the two phenotypes when exposed to stressors, with RLA and RHA rats displaying reactive vs. proactive coping, respectively. In control rats, the WB analysis showed lower hippocampal CB1R relative levels in RLA rats than in their RHA counterparts. After FS, RLA rats showed increased CB1R levels in the dorsal HC (dHC) vs. no change in the ventral HC (vHC), while RHA rats displayed no change in the dHC vs. a decrease in the vHC. In the tissue sections from dHC, FS elicited an increment over the control level of CB1R-like immunoreactivity (LI) in the CA1 and CA3 sectors of the Ammon's horn of RLA rats, while in RHA rats the density of CB1R-LI increased only in the CA1 sector. In tissue sections from the vHC, FS caused an increase over the control values of CB1R-LI only in the CA1 sector of RLA rats and a decrement of the CB1R-LI in the CA1 sector and dentate gyrus of control RHA rats. This study shows for the first time that, in baseline conditions, the CB1Rs are present in the dHC and the vHC of the Roman rat lines with a different distribution along the septo-temporal extension of the HC and that the FS induces rapid and distinct changes in the hippocampal expression of CB1R of RLA vs. RLA rats, in keeping with the view that endocannabinoid signaling may contribute to the molecular mechanisms that regulate the different responses of the dHC vs. the vHC to aversive situations in male Roman rats. Our results also provide evidence supporting the involvement of CB1R in the molecular underpinnings of the susceptibility of RLA rats and the resistance of RHA rats to stress-induced depression-like behavior.