The CB1 Receptor as an Important Mediator of Hedonic Reward Processing

Abstract

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.

Involvement of the dorsomedial prefrontal cortex in high-fat food conditioning in adolescent mice

“…In contrast, the expression of the Cb1r gene appears to be unaltered in NON-EXT animals. This data is rather unexpected as Cb1 receptors participate at cortical level in sensory perception of food [33,34] and also as positive reinforcer [35]. The lack of effect in Cart expression in the CPF [36] is coherent with the apparent low sensitivity of this gene to drugs of abuse previously reported [37].…”

Neurobiological Interactions Between Stress and the Endocannabinoid System

“…Given that the physiological actions of cannabis are mediated by activation of the CB1 receptor, this suggested that a normative function of the eCB system could be to dampen or buffer against the effects of stress. Consistent with this hypothesis, pharmacological or genetic disruption of eCB signaling reliably produces a neurobehavioral phenotype, which directly parallels the classical manifestation of a stress response, including activation of the HPA axis, increased anxiety, suppressed feeding behavior, reduced responsiveness to rewarding stimuli, hypervigilance and arousal, enhanced grooming behavior, and impaired cognitive flexibility (Bellocchio et al, 2013;Friemel et al, 2014;Haller et al, 2004;Marsicano et al, 2002;Patel et al, 2004;Sanchis-Segura et al, 2004;Santucci et al, 1996;Shonesy et al, 2014;Tallett et al, 2007;Varvel and Lichtman, 2002). As such, these data indicate that there is a prominent stressinhibitory role of the eCB system.…”

Sexually-dimorphic alterations in cannabinoid receptor density depend upon prenatal/early postnatal history

“…Intra-accumbal injections of cannabinoid agonists can produce conditioned place preference like morphine (Karimi et al, 2013). Neuroplastic changes in nucleus accumbens following training with highly palatable food have been shown to rely on the CB1R (Guegan et al, 2013) and striatal CB1Rs play a role in the emotional consequences of stress and rewarding experiences (DeChiara et al, 2010a) as well as hedonic reward processing (Friemel et al, 2014). In addition, voluntary activity and sucrose consumption enhance CB1R sensitivity in the striatum (DeChiara et al, 2010b).…”