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.
TY - JOUR
T1 - Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat.
AU - Wakley,Alexa A,
AU - Wiley,Jenny L,
AU - Craft,Rebecca M,
Y1 - 2014/08/02/
PY - 2014/03/26/received
PY - 2014/07/21/revised
PY - 2014/07/24/accepted
PY - 2014/8/19/entrez
PY - 2014/8/19/pubmed
PY - 2015/9/17/medline
KW - Antinociception
KW - Cannabinoid
KW - Estrous cycle
KW - Locomotion
KW - Pain
KW - Sex differences
SP - 22
EP - 8
JF - Drug and alcohol dependence
JO - Drug Alcohol Depend
VL - 143
N2 - 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.
SN - 1879-0046
UR - https://www.unboundmedicine.com/medline/citation/25131716/Sex_differences_in_antinociceptive_tolerance_to_delta_9_tetrahydrocannabinol_in_the_rat_
DB - PRIME
DP - Unbound Medicine
ER -
