title: Corticosteroid dependent and independent effects of a cannabinoid agonist on core temperature, motor activity, and prepulse inhibition of the acoustic startle reflex in Wistar rats.
abstract: BACKGROUND
  There are inconsistent reports on the effects of cannabinoid agonists on prepulse inhibition of the startle reflex (PPI) with increases, decreases, and no effects. It has been hypothesized that the conflicting observations may be as a result of modulation of the effects of cannabinoid agonists by the regulation of corticosteroid release.
  
  
  OBJECTIVE
  The purpose of the present study was to determine the effects of CP55940, a cannabinoid agonist, and metyrapone, a corticosteroid synthesis inhibitor on core temperature, motor activity, the startle reflex, and PPI.
  
  
  METHODS
  Startle responses were measured in 64 male Wistar rats while varying startling stimulus intensities, analogous to dose-response curves. A stimulus potency measure (ES(50)) and a response measure, the maximal achievable response (R                            (MAX)) were derived from the stimulus-response curves.
  
  
  RESULTS
  CP55940 reduced core temperature and motor activity; these effects were potentiated by metyrapone. CP55940 increased R                            (MAX) of startle in the absence of a prepulse by a corticosteroid-dependent mechanism but decreased it when metyrapone was administered before CP55940, a corticosteroid-independent mechanism. The inverse of stimulus potency (ES(50)) was not affected by either drug alone but was increased by the combined drugs. CP55940 increased the prepulse motor gating effects and decreased the prepulse sensory gating effects of the same prepulses but only when given after metyrapone.
  
  
  CONCLUSIONS
  The most parsimonious interpretation of these effects is that CP55940 has some effects through corticosteroid-dependent actions and opposite effects by corticosteroid-independent actions. These two putative sites of actions affect stimulus gating opposite to their effects on response gating.
authors.affiliation: Centre for Clinical Research in Neuropsychiatry, Graylands Hospital, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Avdesh
authors.initials: A
authors.lastname: Avdesh
authors.forename: Vincent
authors.initials: V
authors.lastname: Cornelisse
authors.forename: Mathew Thomas
authors.initials: MT
authors.lastname: Martin-Iverson
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D063386:Cannabinoid Receptor Agonists; D003511:Cyclohexanols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007266:Inhibition, Psychological; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects*
chemical_list: D063386:Cannabinoid Receptor Agonists; D003511:Cyclohexanols; D004791:Enzyme Inhibitors; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D008797:Metyrapone