Differential anxiogenic, aversive, and locomotor effects of THC in adolescent and adult rats
- 901 Downloads
Unpleasant side effects of drugs of abuse often limit their repeated use; however, such effects may be attenuated in adolescents compared to adults.
We investigated whether the anxiogenic, aversive, or locomotor effects of delta-9-tetrahydrocannabinol (THC) differ between adolescent and adult rats.
We used the elevated plus maze (EPM) and light-dark tests of anxiety, the conditioned taste aversion and conditioned place aversion (CPA) tests of generalized aversion, and measures of stress hormone levels in serum to examine effects of THC in adolescent and adult rats. Locomotor activity was also recorded in the EPM, light-dark task, and CPA association sessions.
In the EPM and light-dark tasks, THC was anxiogenic in both age groups, but the drug was more anxiogenic in adults than in adolescents. In the place and taste aversion tasks, THC was aversive in both ages, and at 1.25 and 5 mg/kg, was more aversive in adults than in adolescents. The locomotor response to THC, as measured in the anxiety tasks and CPA, affected adults more than adolescents. Multiple measures revealed a locomotor-decreasing effect in adults, whereas some measures suggested a small locomotor-increasing effect in adolescent rats.
These results suggest that THC can have greater anxiogenic, aversive, and locomotor-reducing effects in adult rats than in adolescent rats. These findings suggest an explanation for reduced marijuana use in adult humans compared to teenagers.
KeywordsTHC Anxiety Aversion HPA axis Adolescent Rat ACTH Dose-response Elevated plus maze Light-dark
The authors wish to thank Reynold Francis for expert technical assistance. This work was funded by DA019346 to Dr. Swartzwelder and by VA Senior Research Career Scientist awards to Drs. Swartzwelder and Wilson.
- APA (1994) Diagnostic and statistical manual for mental disorders. American Psychiatric AssociationGoogle Scholar
- Haertzen CA, Kocher TR, Miyasato K (1983) Reinforcements from the first drug experience can predict later drug habits and/or addiction: results with coffee, cigarettes, alcohol, barbiturates, minor and major tranquilizers, stimulants, marijuana, hallucinogens, heroin, opiates and cocaine. Drug Alcohol Depend 11:147–165PubMedCrossRefGoogle Scholar
- Phillips TJ, Broadbent J, Burkhart-Kasch S, Henderson C, Wenger CD, McMullin C, McKinnon CS, Cunningham CL (2005) Genetic correlational analyses of ethanol reward and aversion phenotypes in short-term selected mouse lines bred for ethanol drinking or ethanol-induced conditioned taste aversion. Behav Neurosci 119:892–910PubMedCrossRefGoogle Scholar
- Schramm-Sapyta NL, Pratt AR, Winder DG (2004) Effects of periadolescent versus adult cocaine exposure on cocaine conditioned place preference and motor sensitization in mice. Psychopharmacology (Berl) 84:344–352Google Scholar
- Schramm-Sapyta NL, Morris RW, Kuhn CM (2006) Adolescent rats are protected from the conditioned aversive properties of cocaine and lithium chloride. Pharmacol Biochem Behav 173:41–48Google Scholar