A behavioural model to reveal place preference to delta 9-tetrahydrocannabinol in mice

Psychopharmacology (Berl). 2000 Jan;147(4):436-8. doi: 10.1007/s002130050013.


Rationale: The rewarding properties of delta 9-tetrahydrocannabinol (THC) are difficult to demonstrate in rodents using standard procedures.

Objective: To evaluate the motivational responses of THC in the place conditioning paradigm in mice after minimizing the dysphoric effects of the first drug exposure and/or the consequences of its pharmacokinetic properties.

Methods: Mice were conditioned to THC (1 or 5 mg/kg) using an unbiased procedure with an elevated number of pairings and long conditioning time.

Results: A place aversion was observed with 5 mg/kg THC using a standard protocol. Similar results were obtained when the CB-1 receptor antagonist SR 141716A (1 mg/kg) was administered immediately after each THC conditioning period. However, mice receiving a priming THC injection and conditioned 24 h later showed a place preference with 1 mg/kg THC and no effect with 5 mg/kg THC.

Conclusion: THC produces a clear place preference in mice by using a long period of conditioning and avoiding the possible dysphoric consequences of the first drug exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Conditioning, Operant / drug effects*
  • Dronabinol / antagonists & inhibitors
  • Dronabinol / pharmacokinetics
  • Dronabinol / pharmacology*
  • Half-Life
  • Hallucinogens / antagonists & inhibitors
  • Hallucinogens / pharmacokinetics
  • Hallucinogens / pharmacology*
  • Male
  • Mice
  • Motivation
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Receptors, Cannabinoid
  • Receptors, Drug / antagonists & inhibitors
  • Reward
  • Rimonabant


  • Hallucinogens
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Dronabinol
  • Rimonabant