title: Cocaine self-administration differentially modulates the expression of endogenous cannabinoid system-related proteins in the hippocampus of Lewis vs. Fischer 344 rats.
abstract: The endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) are modulators of glutamate and γ-aminobutyric acid (GABA), two transmitters involved in cocaine addiction. However, little is known on the effects of cocaine on the enzymes that produce and degrade endocannabinoids. The present work addresses the effects of cocaine self-administration on the immunohistochemical expression of endocannabinoid signalling (ECS)-related proteins in the hippocampus. The study has been performed on two different strains of rats, Lewis (Lew) and Fischer 344 (F344), which are characterized for displaying a differential sensitivity to cocaine, thus making them suitable in the study of vulnerability to drug addiction. Both strains showed differences in the expression of ECS-related proteins in the hippocampus, i.e. Lew rats exhibited lower CB1 expression but higher CB2 expression than F344 rats. After setting similar cocaine self-administration, both strains showed clear differences in the expression of ECS-related proteins, which were differentially restricted to either the 2-AG or anandamide signalling pathways in a self-administration training/drug-dependent manner. The decreases observed in CB1 expression and N-acyl phosphatidylethanolamine phospholipase D:fatty acid amino hydrolase ratio after saline self-administration were enhanced only in cocaine self-administered Lew rats. CB2 expression increase and diacylglycerol lipase α:monoacylglycerol lipase ratio decrease detected after saline self-administration were blocked only in cocaine self-administered F344 rats. These findings indicate that cocaine may regulate hippocampal GABA/glutamate synapses by directly modulating endocannabinoid production/degradation enzymes and that these actions are strain-dependent. This differential response suggests that the endogenous cannabinoid system might contribute to genotype/strain differences on the sensitivity to self-administration training and cocaine addiction.
authors.affiliation: Laboratorio de Medicina Regenerativa, Hospital Carlos Haya (Pabellón de Gobierno), IBIMA, Málaga, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rivera
authors.forename: Miguel
authors.initials: M
authors.lastname: Miguéns
authors.forename: Santiago M
authors.initials: SM
authors.lastname: Coria
authors.forename: Leticia
authors.initials: L
authors.lastname: Rubio
authors.forename: Alejandro
authors.initials: A
authors.lastname: Higuera-Matas
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Bermúdez-Silva
authors.forename: Fernando Rodríguez
authors.initials: FR
authors.lastname: de Fonseca
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
authors.forename: Emilio
authors.initials: E
authors.lastname: Ambrosio
mesh_terms: D000581:Amidohydrolases; D000818:Animals; D001095:Arachidonic Acids; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D063388:Endocannabinoids / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005989:Glycerides; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D012646:Self Administration; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013045:Species Specificity; D013997:Time Factors; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D063388:Endocannabinoids; D005989:Glycerides; D008071:Lipoprotein Lipase; D008994:Monoacylglycerol Lipases; D010739:Phospholipase D; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate; C527163:Napepld protein, rat