title: Effects of acute and repeated dosing of the synthetic cannabinoid CP55,940 on intracranial self-stimulation in mice.
abstract: BACKGROUND
  Synthetic cannabinoids have emerged as a significant public health concern. To increase the knowledge of how these molecules interact on brain reward processes, we investigated the effects of CP55,940, a high efficacy synthetic CB1 receptor agonist, in a frequency-rate intracranial self-stimulation (ICSS) procedure.
  
  
  METHODS
  The impact of acute and repeated administration (seven days) of CP55,940 on operant responding for electrical brain stimulation of the medial forebrain bundle was investigated in C57BL/6J mice.
  
  
  RESULTS
  CP55,940 attenuated ICSS in a dose-related fashion (ED50 (95% C.L.)=0.15 (0.12-0.18)mg/kg). This effect was blocked by the CB1 receptor antagonist rimonabant. Tolerance developed quickly, though not completely, to the rate-decreasing effects of CP55,940 (0.3mg/kg). Abrupt discontinuation of drug did not alter baseline responding for up to seven days. Moreover, rimonabant (10mg/kg) challenge did not alter ICSS responding in mice treated repeatedly with CP55,940.
  
  
  CONCLUSIONS
  The finding that CP55,940 reduced ICSS in mice with no evidence of facilitation at any dose is consistent with synthetic cannabinoid effects on ICSS in rats. CP55,940-induced ICSS depression was mediated through a CB1 receptor mechanism. Additionally, tolerance and dependence following repeated CP55,940 administration were dissociable. Thus, CP55,940 does not produce reward-like effects in ICSS under these conditions.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, PO Box 980613, Richmond, 23298-0613, VA U.S.A. Electronic address: grimtw@vcu.edu.
authors.forename: Travis W
authors.initials: TW
authors.lastname: Grim
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, PO Box 980613, Richmond, 23298-0613, VA U.S.A.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Wiebelhaus
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, PO Box 980613, Richmond, 23298-0613, VA U.S.A.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Morales
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, PO Box 980613, Richmond, 23298-0613, VA U.S.A.
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, PO Box 980613, Richmond, 23298-0613, VA U.S.A.
authors.forename: Aron H
authors.initials: AH
authors.lastname: Lichtman
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D003216:Conditioning, Operant / Q000187:drug effects; D003511:Cyclohexanols / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D051379:Mice; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors; D012201:Reward; D000077285:Rimonabant; D012653:Self Stimulation / Q000187:drug effects*
chemical_list: D003511:Cyclohexanols; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000077285:Rimonabant
keywords: CP55,940; Dependence; Intracranial self-stimulation; Mice; Synthetic cannabinoid; Tolerance; withdrawal