title: Gonadal hormones do not alter the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol in adult rats.
abstract: The purpose of this study was to determine whether sex differences in the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) are due to activational effects of gonadal hormones. Rats were sham-gonadectomized (sham-GDX) or gonadectomized (GDX). GDX females received no hormone replacement (GDX+0), estradiol (GDX+E2), progesterone (GDX+P4), or both (GDX+E2/P4). GDX male rats received no hormone (GDX+0) or testosterone (GDX+T). Two weeks later, antinociceptive potency of THC was determined (pre-chronic test) on the warm water tail withdrawal and paw pressure assays. Vehicle or a sex-specific THC dose (females, 5.7mg/kg, males, 9.9mg/kg) was administered twice-daily for 9days, then the THC dose-effect curves were re-determined (post-chronic test). On the pre-chronic test (both assays), THC was more potent in sham-GDX females than males, and gonadectomy did not alter this sex difference. In GDX females, P4 significantly decreased THC's antinociceptive potency, whereas E2 had no effect. In GDX males, T did not alter THC's antinociceptive potency. After chronic THC treatment, THC's antinociceptive potency was decreased more in sham-GDX females than males, on the tail withdrawal test; this sex difference in tolerance was not altered in GDX or hormone-treated groups. These results suggest that greater antinociceptive tolerance in females, which occurred despite females receiving 40% less THC than males, is not due to activational effects of gonadal hormones.
authors: Department of Psychology, WA State University, USA.
authors: Alexa A
authors: AA
authors: Wakley
authors: RTI International, USA.
authors: Jenny L
authors: JL
authors: Wiley
authors: Department of Psychology, WA State University, USA. Electronic address: craft@wsu.edu.
authors: Rebecca M
authors: RM
authors: Craft
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004361:Drug Tolerance; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010147:Pain Measurement; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D013759:Dronabinol
keywords: Cannabinoid; Estradiol; Progesterone; Sex differences; Testosterone