Interactions between endocannabinoids and stress-induced decreased sensitivity to natural reward

Abstract

Since endocannabinoids modulate reward processing and the stress response, we tested the hypothesis that endocannabinoids regulate stress-induced decreased sensitivity to natural reward. Restraint was used to produce stress-induced reductions in sucrose consumption and preference in male mice. Central cannabinoid receptor (CB 1 ) signaling was modulated pharmacologically prior to the application of stress. The preference for sucrose over water was significantly decreased in mice exposed to restraint. Treatment of mice with a cannabinoid receptor agonist (CP55940) or fatty acid amide hydrolase inhibitor (URB597) attenuated, while the CB 1 receptor antagonist/inverse agonist, rimonabant (SR141716), enhanced, stress-induced decreases in sucrose preference. These data are consistent with a tonically active, stress-inhibitory role for the CB 1 receptor. Mice treated with 10 daily episodes of restraint showed reduced sucrose preference that was unaffected by CP55940 and URB597. However, rimonabant produced a greater reduction in sucrose preference on day 10 compared to day 1. These data suggest that on day 10, endocannabinoid signaling is maximally activated and essential for reward sensitivity. The findings of the present study indicate that the CB 1 /endocannabinoid signaling system is an important allostatic mediator that both modulates the responses of mice to stress and is itself modulated by stress.

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

“…Blenov and colleagues used mice, and alcohol was available daily. There are also studies showing that environmental stress can markedly affect endocannabinoid neurotransmission (Hill et al 2006;Patel et al 2005;Rademacher and Hillard 2007), and thus it can be speculated that different responses to the blockade of FAAH may also depend on the endogenous tone of the system at the moment of drug administration.…”

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

“…At the most effective dose for reducing alcohol intake, URB597 has no effect on sucrose or saccharin preference in alcohol naïve mice, but increases sucrose preference in mice after alcohol withdrawal [Zhou et al, 2017c]. In previous work, URB597 is found to increase sucrose preference in stress-exposed animals, probably due to its "antidepression" properties [Rademacher and Hillard, 2007;Bortolato et al, 2007]. Consistent with studies on cocaine, nicotine and opioid seeking behaviour [Panlilio et al, 2013;Sloan et al, 2017], our findings show initial, promising data that FAAH inhibitors decrease alcohol excessive drinking, and "relapse" drinking in both male and female mice.…”

Cross-sensitization and cross-tolerance between exogenous cannabinoid antinociception and endocannabinoid-mediated stress-induced analgesia

“…Considering the importance of this endogenous system in regulating neuronal excitability (Chevaleyre and Castillo, 2003;Monory et al, 2006) as well as nociception, learning, memory, and appetitive motivation (Freund et al, 2003;Hill et al, 2005;Hohmann et al, 2005;Lichtman et al, 2002;Rademacher and Hillard, 2007), disruptions in endocannabinoid transmission could have a far-reaching, adverse impact. For example, the endocannabinoid system regulates extinction of aversive memories (Marsicano et al, 2002) through a habituation-like process (Kamprath et al, 2006).…”