Differential anxiogenic, aversive, and locomotor effects of THC in adolescent and adult rats

Abstract

Rationale

Unpleasant side effects of drugs of abuse often limit their repeated use; however, such effects may be attenuated in adolescents compared to adults.

Objectives

We investigated whether the anxiogenic, aversive, or locomotor effects of delta-9-tetrahydrocannabinol (THC) differ between adolescent and adult rats.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgment

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.

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Correspondence to Cynthia M. Kuhn.

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Schramm-Sapyta, N.L., Cha, Y.M., Chaudhry, S. et al. Differential anxiogenic, aversive, and locomotor effects of THC in adolescent and adult rats. Psychopharmacology 191, 867–877 (2007). https://doi.org/10.1007/s00213-006-0676-9

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Keywords

  • THC
  • Anxiety
  • Aversion
  • HPA axis
  • Adolescent
  • Rat
  • ACTH
  • Dose-response
  • Elevated plus maze
  • Light-dark