Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcohol use disorders (AUDs) have a high incidence of co-morbidity with stress-related psychopathologies, such as post-traumatic stress disorder (PTSD). Genetic and pharmacological studies support a prominent role for the endocannabinoid system (ECS) in modulating stress-related behaviors relevant to AUDs and PTSD. Mouse lines selectively bred for high (HAP) and low (LAP) alcohol preference show reproducible differences in fear-potentiated startle (FPS), a model for PTSD-related behavior. The first experiment in this study assessed levels of the endocannabinoids, anandamide (AEA) and sn-2 arachidonylglycerol (2-AG), in the prefrontal cortex (PFC), amygdala (AMG), and hippocampus (HIP) of male and female HAP1 and LAP1 mice following the expression of FPS to determine whether ECS responses to conditioned-fear stress (FPS) were correlated with genetic propensity toward high or low alcohol preference. The second experiment examined effects of a cannabinoid receptor type 1 agonist (CP55940) and antagonist (rimonabant) on the expression of FPS in HAP1 and LAP1 male and female mice. The estrous cycle of females was monitored throughout the experiments to determine if the expression of FPS differed by stage of the cycle. FPS was greater in male and female HAP1 than LAP1 mice, as previously reported. In both experiments, LAP1 females in diestrus displayed greater FPS than LAP1 females in metestrus and estrus. In the AMG and HIP, AEA levels were greater in male fear-conditioned HAP1 mice than LAP1 mice. There were no line or sex differences in effects of CP55940 or rimonabant on the expression of FPS. However, surprisingly, evidence for anxiogenic effects of prior treatment with CP55940 were seen in all mice during the third drug-free FPS test. These findings suggest that genetic differences in ECS function in response to fear-conditioning stress may underlie differences in FPS expression in HAP1 and LAP1 selected lines.
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PMID:Endocannabinoids and Fear-Related Behavior in Mice Selectively Bred for High or Low Alcohol Preference. 3156 80

Alcohol consumption may precede, or result from, behavioral inflexibility and contribute to individuals' difficulties ceasing drinking. Attentional set shifting tasks are an animal analog to a human behavioral flexibility task requiring recognition of a previous strategy as inappropriate, and the formation and maintenance of a novel strategy (Floresco, Block, & Tse, 2008). Abstinent individuals with alcohol use disorder, nonalcoholic individuals with a family history of alcoholism, and mice exposed to chronic-intermittent alcohol vapor show impaired behavioral flexibility (Gierski et al., 2013; Hu, Morris, Carrasco, & Kroener, 2015; Oscar-Berman et al., 2009). Behavioral flexibility deficits can be linked to frontal cortical regions connected to the striatum (Ragozzino, 2007), and alterations to the endocannabinoid system, implicated in drug seeking and consumption (Economidou et al., 2006; Serrano & Parsons, 2011), may affect these behaviors. Alcohol-preferring and nonpreferring rodents exhibit differences in CB1 receptor expression (CB1R; Hansson et al., 2007; Hungund & Basavarajappa, 2000), but whether dorsal striatal CB1Rs are important for other alcohol-related behaviors such as attentional set shifting tasks remains unclear. This study assesses whether selectively bred high (HAP) versus low alcohol-preferring mice differ in an operant attentional set shifting task or CB1R levels in the dorsal striatum and whether a history of voluntary alcohol consumption in crossed HAP mice exacerbates inflexibility. Contrary to our hypothesis, neither genetic differences in alcohol preference nor drinking affected set shifting. However, high alcohol-preferring mice-3 mice showed reduced levels of dorsal striatal CB1R compared with low alcohol-preferring-3 mice, suggesting that genetic differences in alcohol consumption may be mediated in part by striatal CB1R. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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PMID:Attentional set shifting in HAP3, LAP3, and cHAP mice is unaffected by either genetic differences in alcohol preference or an alcohol drinking history. 3215 Apr 28