title: Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat.
abstract: BACKGROUND
  Sex differences in cannabinoid effects have been reported in rodents, with adult females typically being more sensitive than adult males. The present study compared the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) in adult, gonadally intact female vs. male rats.
  
  
  METHODS
  Cumulative dose-effect curves were obtained for THC (1.0-18 mg/kg i.p.) on warm water tail withdrawal and paw pressure tests. Vehicle or the sex-specific ED80 dose for THC was administered twice daily for 9 days; THC dose-effect curves were then re-determined.
  
  
  RESULTS
  On the pre-chronic test day, THC was significantly more potent in females than males in producing antinociception on the tail withdrawal and paw pressure tests. After 9 days of twice-daily THC treatment (5.4 mg/kg/injection in females and 7.6 mg/kg/injection in males), THC potency on both tests decreased more in females than males. On the tail withdrawal test, chronic THC produced 4.2- vs. 2.8-fold increases in ED50 values in females vs. males, respectively. On the paw pressure test, chronic THC produced 4.4- vs. 2.9-fold increases in ED50 values in females vs. males, respectively. Chronic THC treatment did not significantly disrupt estrous cycling in females.
  
  
  CONCLUSIONS
  These results demonstrate that--even when sex differences in acute THC potency are controlled--females develop more antinociceptive tolerance to THC than males. Given the importance of drug tolerance in the development of drug dependence, these results suggest that females may be more vulnerable than males to developing dependence after chronic cannabinoid exposure.
authors.affiliation: Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA.
authors.forename: Alexa A
authors.initials: AA
authors.lastname: Wakley
authors.affiliation: RTI International, Research Triangle Park, NC 27709-2194, USA.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Wiley
authors.affiliation: Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA. Electronic address: craft@wsu.edu.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Craft
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002375:Catalepsy / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004361:Drug Tolerance; D030762:Estrous Cycle; D005260:Female; D008124:Locomotion / Q000187:drug effects; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D012727:Sex Characteristics
chemical_list: D000700:Analgesics; D013759:Dronabinol
keywords: Antinociception; Cannabinoid; Estrous cycle; Locomotion; Pain; Sex differences