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Temporal and Behavioral Variability in Cannabinoid Receptor Expression in Outbred Mice Submitted to Ethanol‐Induced Locomotor Sensitization Paradigm
Author(s) -
Coelhoso Cássia C.,
Engelke Douglas S.,
Filev Renato,
Silveira Dartiu X.,
Mello Luiz E.,
SantosJunior Jair G.
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12130
Subject(s) - cannabinoid receptor , cannabinoid , sensitization , endocannabinoid system , prefrontal cortex , hippocampus , striatum , ventral tegmental area , medicine , psychology , neuroscience , endocrinology , pharmacology , chemistry , receptor , dopamine , agonist , cognition , dopaminergic
Background There is a close relationship between the endocannabinoid system and alcoholism. This study investigated possible differential expression of cannabinoid receptors CB 1 ( CB 1 R ) and CB 2 ( CB 2R) in an outbred mice strain displaying behavioral variability to ethanol ( E t OH )‐induced locomotor sensitization. Methods Male adult S wiss mice treated chronically with E t OH (2 g/kg, i.p., daily for 21 days) were classified as “ E t OH _High” or “ E t OH _Low” according to their locomotor activity after the 21st E t OH injection. A control group was similarly injected with saline. Temporal analysis of CB 1 R and CB 2 R immunoreactivity was performed in 3 different occasions: (i) at the end of chronic E t OH treatment, (ii) on the fifth day of E t OH withdrawal, and (iii) after E t OH challenge. Results Overall, no differences were seen between experimental groups regarding the CB 1 R at the end of acquisition. However, there were decreases in CB 2 R in the prefrontal cortex and the hippocampus in E t OH _Low mice. On the fifth day of withdrawal, only E t OH _High mice presented increase in CB 1 R . Nonetheless, CB 2 R up‐regulation was observed in both E t OH _High and E t OH _Low mice. E t OH challenge counteracted CB 1 R and CBR 2 up‐regulation, mainly in the E t OH _High, in structures related to emotionality, such as prefrontal cortex, ventral tegmental area, amygdala, striatum, and hippocampus. Conclusions There are different patterns of cannabinoid receptor expression during locomotor sensitization paradigm, at both temporal and behavioral perspectives. We hypothesize that CB 2 R down‐regulation might be related to resilience to develop locomotor sensitization, while CB 1 R up‐regulation relates to withdrawal aspects in sensitized mice.