Assessment of the rewarding effects of dimenhydrinate using the conditioned place preference paradigm in mice

Dimenhydrinate (DIM) is an over-the-counter antihistamine consisting of diphenhydramine (DIP) and 8-chlorotheophylline (CTP). Medical use of DIM is for prevention of nausea and motion sickness. Recently, it has been reported that DIM may be used alone or in combination with other drugs for recreational purposes due to its euphoric and hallucinogenic effects. To investigate the putatively rewarding properties of DIM and its constituents DIP and CTP, we used a conditioned place preference (CPP) test in mice. DIM significantly induced CPP at a dose of 30 mg/kg. Neither DIP (3, 10, and 30 mg/kg) nor CTP (3, 10, and 30 mg/kg) alone induced CPP. Because neither DIP nor CTP resulted in CPP, the rewarding property of DIM appears to be caused by the sum of the effects of its constituents. In addition, low doses of DIM (3 mg/kg), co-administered with low doses of cocaine (7.5 mg/kg), significantly induced CPP, while neither low-dose DIM (3 mg/kg) nor low-dose cocaine (7.5 mg/kg) administered separately induced CPP. This result suggests the liability of DIM use in combination with other abused drugs to create a stronger effect.