title: Statistical parametric mapping reveals regional alterations in cannabinoid CB1 receptor distribution and G-protein activation in the 3D reconstructed epileptic rat brain.
abstract: OBJECTIVE
  The endocannabinoid system is known to modulate seizure activity in several in vivo and in vitro models, and CB(1) -receptor activation is anticonvulsant in the rat pilocarpine model of acquired epilepsy (AE). In these epileptic rats, a unique redistribution of the CB(1) receptor occurs within the hippocampus; however, an anatomically inclusive analysis of the effect of status epilepticus (SE)-induced AE on CB(1) receptors has not been thoroughly evaluated. Therefore, statistical parametric mapping (SPM), a whole-brain unbiased approach, was used to study the long-term effect of pilocarpine-induced SE on CB(1) -receptor binding and G-protein activation in rats with AE.
  
  
  METHODS
  Serial coronal sections from control and epileptic rats were cut at equal intervals throughout the neuraxis and processed for [(3) H]WIN55,212-2 (WIN) autoradiography, WIN-stimulated [(35) S]GTPγS autoradiography, and CB(1) -receptor immunohistochemistry (IHC). The autoradiographic techniques were evaluated with both region of interest (ROI) and SPM analyses.
  
  
  RESULTS
  In rats with AE, regionally specific increases in CB(1) -receptor binding and activity were detected in cortex, discrete thalamic nuclei, and other regions including caudate-putamen and septum, and confirmed by IHC. However, CB(1) receptors were unaltered in several brain regions, including substantia nigra and cerebellum, and did not exhibit regional decreases in rats with AE.
  
  
  CONCLUSIONS
  This study provides the first comprehensive evaluation of the regional distribution of changes in CB(1) -receptor expression, binding, and G-protein activation in the rat pilocarpine model of AE. These regions may ultimately serve as targets for cannabinomimetic compounds or manipulation of the endocannabinoid system in epileptic brain.
authors.affiliation: Department of Anatomy & Neurobiology, Virginia Commonwealth University, Richmond, VA, U.S.A.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Sayers
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nguyen
authors.forename: Robert E
authors.initials: RE
authors.lastname: Blair
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Sim-Selley
authors.forename: Robert J
authors.initials: RJ
authors.lastname: DeLorenzo
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D048588:Benzoxazines / Q000493:pharmacokinetics; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D001931:Brain Mapping; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D021621:Imaging, Three-Dimensional; D008297:Male; D009025:Morpholines / Q000493:pharmacokinetics; D009281:Naphthalenes / Q000493:pharmacokinetics; D010862:Pilocarpine / Q000633:toxicity; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D013460:Sulfur Isotopes / Q000493:pharmacokinetics; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D000927:Anticonvulsants; D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; D013460:Sulfur Isotopes; D010862:Pilocarpine; D014316:Tritium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D019204:GTP-Binding Proteins; D003975:Diazepam