title: Chronic WIN55,212-2 elicits sustained and conditioned increases in intracranial self-stimulation thresholds in the rat.
abstract: The present study sought to examine whether repeated administration of the CB(1) receptor agonist WIN55,212-2 affected intracranial self-stimulation (ICSS) behavior and induced phenomena of tolerance or sensitization, similar to typical addictive drugs. Rats received intraperitoneal injections of vehicle for 5 days, vehicle or WIN55,212-2 (0.1, 0.3 or 1mg/kg) for 20 subsequent days, and vehicle for 5 additional days. Thresholds for ICSS were measured before and after each injection. The initial five injections of vehicle did not affect ICSS thresholds. WIN55,212-2 (1mg/kg) significantly increased ICSS thresholds from the first day of administration, an effect that remained stable across the subsequent days of administration. During the 5 additional days, where WIN55,212-2 was substituted with vehicle, rats demonstrated a conditioned increase in postinjection thresholds that was significant the first 3 days of this period. These findings indicate that repeated WIN55,212-2 administration elicited a sustained increase in ICSS, i.e., phenomena of tolerance or sensitization were not observed. The present data demonstrate cannabinoid-predictive stimuli that may gain affective salience and play an important role in maintaining cannabinoid administration.
authors.affiliation: Department of Psychology, University of Crete, 74100 Rethymno, Crete, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Mavrikaki
authors.forename: Eirini
authors.initials: E
authors.lastname: Markaki
authors.forename: George G
authors.initials: GG
authors.lastname: Nomikos
authors.forename: George
authors.initials: G
authors.lastname: Panagis
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines / Q000494:pharmacology*; D001703:Biophysics / Q000379:methods; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004558:Electric Stimulation / Q000379:methods; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012653:Self Stimulation / Q000187:drug effects* / Q000502:physiology*; D012684:Sensory Thresholds / Q000187:drug effects
chemical_list: D048588:Benzoxazines; D002121:Calcium Channel Blockers; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone