Dimenhydrinate produces a conditioned place preference in rats

Pharmacol Biochem Behav. 2003 Apr;75(1):173-9. doi: 10.1016/s0091-3057(03)00068-6.


Dimenhydrinate (DMH; trade names Gravol and Dramamine) is a compound of diphenhydramine (DP) and 8-chlorotheophylline in equimolar ratios. DMH has been reported to be abused by humans for its euphoric and hallucinogenic properties but few studies have evaluated its reinforcing effects in animals. To evaluate the hypothesis that DMH and its constituents DP and 8-chlorotheophylline are rewarding in animals, rats were tested for conditioned place preference (CPP). The paradigm consisted of pre-exposure (three 15-min sessions of access to both sides of the chamber), conditioning [eight 30-min pairings of one side with drug (four sessions) and, on alternate days, the other side with vehicle (four sessions)] and test phases (three 15-min sessions of access to both sides of the chamber). Significant preferences for the drug-paired location were found on test session one after conditioning with 60.0, but not 25.0, 40.0 or 50.0 mg/kg of DMH, and after conditioning with 37.8 but not 27.0 or 32.4 mg/kg of DP. No preference was found after conditioning with 23.0, 27.6 or 32.2 mg/kg of 8-chlorotheophylline. All three drugs stimulated locomotor activity during conditioning sessions and DMH and DP showed sensitization over conditioning sessions. DMH doses that showed sensitization (25.0 and 40.0 mg/kg) were lower than the dose (60.0 mg/kg) that produced a CPP revealing a dissociation of locomotor stimulating versus rewarding effects. Results reveal that DMH and DP have rewarding properties, although the molar equivalent dose-response curve for DP appeared to be further to the right than that for DMH. Future investigations into the neurotransmitter systems modulating this effect are awaited.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Operant / drug effects*
  • Dimenhydrinate / pharmacology*
  • Diphenhydramine / pharmacology
  • Dose-Response Relationship, Drug
  • Histamine H1 Antagonists / pharmacology*
  • Male
  • Motor Activity / drug effects
  • Rats
  • Rats, Wistar
  • Theophylline / analogs & derivatives*
  • Theophylline / pharmacology


  • Histamine H1 Antagonists
  • Diphenhydramine
  • Theophylline
  • 8-chlorotheophylline
  • Dimenhydrinate