Abstract
The purpose of this study was to determine whether chronic administration of Δ9-tetrahydrocannabinol (THC) during adolescence would (1) modify any sex-specific effects of THC on learning and (2) affect the development of tolerance to THC as an adult. Male and female rats received daily injections of saline or 5.6 mg/kg of THC from postnatal day 35–75, yielding four groups (female/saline, female/THC, male/saline, and male/THC). Rats were then trained on a procedure that assayed both learning and performance behavior and administered 0.32–18 mg/kg of THC acutely as adults (experiment 1). THC produced rate-decreasing and error-increasing effects in both sexes; however, female rats were more sensitive than male rats were to the rate-decreasing effects. Rats were then chronically administered 10 mg/kg of THC (experiment 2). Rats that received THC during adolescence developed tolerance to the rate-decreasing effects more slowly and less completely than did rats that received saline; in addition, females developed tolerance to the error-increasing effects of THC slower than males did. Western blot analysis of brain tissue indicated long-term changes in hippocampal and striatal cannabinoid type-1 receptor (CB1R) levels despite levels that were indistinguishable immediately after chronic treatment during adolescence. Striatal CB1R levels were increased in adult rats that received THC during adolescence; hippocampal CB1R levels varied by sex. In summary, female rats were more sensitive than male rats were to the acute and chronic effects of THC, and chronic administration of THC during adolescence produced long-term changes in CB1R levels that correlated with decreased tolerance development to the rate-decreasing effects of THC.
Footnotes
- Received June 24, 2015.
- Accepted October 9, 2015.
These data were adapted from the dissertation of Peter F. Weed: Effects of Chronic Δ9-Tetrahydrocannabinol during Adolescence on Adult Repeated Acquisition and Performance Behavior, Tolerance, and CB1 Receptor Expression in Male and Female Rats. In addition, some of these data were previously presented as a poster at the poster presentation: Weed PF (2015) ASPET meeting in Boston, MA, entitled, “Effects of Chronic D9-tetrahydrocannabinol during Adolescence on Adult Repeated Acquisition and Performance Behavior and CB1 Receptor ExpresQ: 2 sion in Male and Female Rats.” 2015 ASPET Conference; Mar 28-Apr 1; Boston, MA. abstract 101699, American Society of Pharmacology and Experimental Therapeutics, Bethesda.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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