title: Assessing addiction vulnerability with different rat strains and place preference procedures: the role of the cocaine and amphetamine-regulated transcript.
abstract: Validated biomarkers of addiction vulnerability are unavailable despite their potential value in diagnostics and therapeutics. As cocaine and amphetamine-regulated transcript (CART) peptides can be considered candidates for such biomarkers, we have studied the acute regulation of CART gene expression in the nucleus accumbens of rats with different drug-seeking behaviors. Two subgroups of Sprague-Dawley rats with different persistences of cocaine-induced and morphine-induced place preference showed a similar regulation of CART mRNA irrespective of their behavioral differences: CART gene expression was unaffected by acute cocaine and downregulated by acute morphine to a similar extent in both subgroups. Fischer 344 and Lewis rats, known to exhibit very different drug-seeking behaviors, showed lower basal expression of CART when compared with Sprague-Dawley rats, being almost undetectable in the case of the Lewis strain. Acute morphine downregulated CART in Fischer 344 rats as it did in Sprague-Dawley rats. The results tend to show that CART mRNA regulation by acute morphine or cocaine in the nucleus accumbens does not seem predictive of addiction vulnerability. However, in the particular case of Lewis rats, the pronounced hypoactivity of the CART system could contribute to the high vulnerability of this strain to develop drug-seeking behaviors.
authors.affiliation: Translational Research Unit, General University Hospital of Ciudad Real, Ciudad Real bFaculty of Pharmacy, CEU San Pablo University, Madrid, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Salas
authors.forename: Carlos
authors.initials: C
authors.lastname: Bocos
authors.forename: Carmen Del
authors.initials: CD
authors.lastname: Castillo
authors.forename: Carmen
authors.initials: C
authors.lastname: Pérez-García
authors.forename: Lidia
authors.initials: L
authors.lastname: Morales
authors.forename: Luis F
authors.initials: LF
authors.lastname: Alguacil
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D058999:Drug-Seeking Behavior / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D009020:Morphine; D003042:Cocaine