Accepted manuscript
Gonadal hormones do not alter the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol in adult rats
Pharmacology, biochemistry and behavior, Vol.133, pp.111-121
06/2015
Handle:
https://hdl.handle.net/2376/112792
PMCID: PMC4430373
PMID: 25863271
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.
•On the pre-chronic test, THC was more potent in sham-GDX females than males.•In GDX females, progesterone decreased THC's antinociceptive potency.•In GDX males, testosterone did not alter THC's antinociceptive potency.•Tolerance to THC was greater in sham-GDX females than males, but this sex difference was not hormone-mediated.
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Details
- Title
- Gonadal hormones do not alter the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol in adult rats
- Creators
- Alexa A Wakley - Department of Psychology, WA State University, USAJenny L Wiley - RTI International, USARebecca M Craft - Department of Psychology, WA State University, USA
- Publication Details
- Pharmacology, biochemistry and behavior, Vol.133, pp.111-121
- Academic Unit
- Psychology, Department of
- Publisher
- Elsevier Inc
- Identifiers
- 99900547780701842
- Language
- English
- Resource Type
- Accepted manuscript