title: Residual effects of focal brain ischaemia upon cannabinoid CB(1) receptor density and functionality in female rats.
abstract: Ischaemic insult results in short-term changes in cannabinoid-1 (CB(1)) receptor expression in the brain, but it is not known whether long-term changes occur, which could potentially mean a change in the intrinsic ability of the brain to withstand new ischaemic episodes. In this study, we have investigated the expression and functionality of CB(1) receptors in coronal brain slices obtained from ovariectomised female rats 46days after middle cerebral artery occlusion (MCAO). The animals were treated with either 17ß-oestradiol or placebo pellets 6h after MCAO and thereafter housed either in isolated or enriched environments. [(3)H]CP55,940 autoradiography indicated no significant effect of 17ß-oestradiol treatment or housing environment upon CB(1) receptor densities. There was, however, a modest but significant decrease in the CB(1) receptor density on the ipsilateral side relative to the contralateral side in the frontal cortex, parietal cortex, CA1-CA3 regions of the hippocampus, thalamus and hypothalamus. CB(1) receptor functionality was assessed by measurement of basal and CP55,940-stimulated [(35)S]GTPγS autoradiography. In the frontal cortex, parietal cortex, CA1-CA3 regions of the hippocampus and dentate gyrus, a robust stimulation, blocked by the CB(1) receptor inverse agonist AM251, was seen. There were no significant changes in the response to CP55,940 with respect either to the 17ß-oestradiol treatment, housing environment or MCAO. Our results reveal that although there are modest long-term decreases in ipsilateral CB(1) receptor densities following MCAO in female rats, these decreases do not result in a functional CB(1) receptor deficit.
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Medicine, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Rojo
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Söderström
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D003511:Cyclohexanols / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013460:Sulfur Isotopes / Q000493:pharmacokinetics; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D003511:Cyclohexanols; D004967:Estrogens; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013460:Sulfur Isotopes; D014316:Tritium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C103505:AM 251; D004958:Estradiol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol