Pharmacological Effects of Acute and Repeated Administration of Δ9-Tetrahydrocannabinol in Adolescent and Adult Rats
- Departments of Pharmacology and Toxicology (J.L.W., M.M.O., M.E.T.) and Psychology (J.L.W., M.J.W.), Virginia Commonwealth University, Richmond, Virginia
- Address correspondence to:
Dr. Jenny Wiley, Department of Pharmacology and Toxicology, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA 23298-0613. E-mail: jwiley{at}vcu.edu
Abstract
Adolescents of many mammalian species exhibit rapid physiological change that is accompanied by behaviors such as increased risk taking and social interaction with peers. Marijuana abusers frequently report that their initial use occurred during adolescence. Our goal was to determine whether the in vivo effects of Δ9-tetrahydrocannabinol (Δ9-THC) differed in adolescent and adult rats. Following initial testing with Δ9-THC in adolescent [postnatal day (PN)29] and adult (>PN60) rats of both sexes, we injected rats twice daily with 10 mg/kg Δ9-THC or vehicle for 9.5 days. Subsequently, rats were again injected with their initial dose of Δ9-THC and tested. In all rats, Δ9-THC produced dose-dependent locomotor suppression, antinociception, hypothermia and catalepsy. Some age-dependent differences in potency and efficacy were noted. Although Δ9-THC dose-effect functions were more similar across age after repeated exposure, subchronic dosing produced greater change in the hypothermic and locomotor effects of Δ9-THC in adolescents, but less change in its antinociceptive effects. These results suggest that the effects of initial exposure to Δ9-THC may not be entirely predictive of the effects of repeated exposure. Despite similarities in pharmacological effects of Δ9-THC after repeated use, adolescents and adults may exhibit differences in the pattern of transition from use to abuse.
Footnotes
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This research was supported by National Institute on Drug Abuse Grant DA-016644 (M.J.W.) and National Institute on Drug Abuse Training Grant DA-07027.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.108126.
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ABBREVIATIONS: PN, postnatal; CB, cannabinoid; Δ9-THC, Δ9-tetrahydrocannabinol; SR141716A, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl; ANOVA, analysis of variance; CL, confidence limits; CP 55,940, (-)-cis-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)phenyl]-trans-4-(3-hydroxy-propyl)cyclohexanol.
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- Received May 21, 2006.
- Accepted December 14, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
