title: Temporal and behavioral variability in cannabinoid receptor expression in outbred mice submitted to ethanol-induced locomotor sensitization paradigm.
abstract: BACKGROUND
  There is a close relationship between the endocannabinoid system and alcoholism. This study investigated possible differential expression of cannabinoid receptors CB1 (CB1R) and CB2 (CB2R) in an outbred mice strain displaying behavioral variability to ethanol (EtOH)-induced locomotor sensitization.
  
  
  METHODS
  Male adult Swiss mice treated chronically with EtOH (2 g/kg, i.p., daily for 21 days) were classified as "EtOH_High" or "EtOH_Low" according to their locomotor activity after the 21st EtOH injection. A control group was similarly injected with saline. Temporal analysis of CB1R and CB2R immunoreactivity was performed in 3 different occasions: (i) at the end of chronic EtOH treatment, (ii) on the fifth day of EtOH withdrawal, and (iii) after EtOH challenge.
  
  
  RESULTS
  Overall, no differences were seen between experimental groups regarding the CB1R at the end of acquisition. However, there were decreases in CB2R in the prefrontal cortex and the hippocampus in EtOH_Low mice. On the fifth day of withdrawal, only EtOH_High mice presented increase in CB1R. Nonetheless, CB2R up-regulation was observed in both EtOH_High and EtOH_Low mice. EtOH challenge counteracted CB1R and CBR2 up-regulation, mainly in the EtOH_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 CB2R down-regulation might be related to resilience to develop locomotor sensitization, while CB1R up-regulation relates to withdrawal aspects in sensitized mice.
authors: Laboratory of Neurobiology , Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors: Cássia C
authors: CC
authors: Coelhoso
authors: Douglas S
authors: DS
authors: Engelke
authors: Renato
authors: R
authors: Filev
authors: Dartiu X
authors: DX
authors: Silveira
authors: Luiz E
authors: LE
authors: Mello
authors: Jair G
authors: JG
authors: Santos-Junior
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D000431:Ethanol / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis* / Q000235:genetics; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000431:Ethanol
keywords: Behavioral Variability; Cannabinoid Receptor; Ethanol Withdrawal; Locomotor Sensitization