Effects of ambient temperature on locomotor activity and place conditioning elicited by abused psychostimulants in mice: Role of 3,4-methylenedioxy moiety.

Abstract

Humans often administer psychostimulants in party or music festival settings characterized by warm ambient temperatures, which may impact drug effects; however, preclinical studies rarely investigate drug effects at multiple ambient temperatures. Work with 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) suggests that the presence of a 3,4-methylenedioxy ring moiety may influence ambient temperature-dependent effects. Locomotor activity and conditioned place preference dose-response curves were generated at 20±2°C for two amphetamine analogues (MDMA and methamphetamine [METH]) and two cathinone analogues (MDPV and α-pyrrolidinopentiophenone [αPVP]) in mice. Effects were then redetermined at 29±2°C for each drug and assay. All four drugs elicited dose-dependent locomotor stimulation at the cool ambient temperature. At the warm ambient temperature, MDMA and MDPV produced sensitization to stereotypy, whereas METH and αPVP produced sensitization to locomotor activity. Regarding place conditioning, the warm ambient environment potentiated place preference elicited by doses of METH and αPVP that were sub-threshold in the cool ambient environment, but attenuated the effects of analogous doses of MDMA and MDPV. These studies suggest that warmer ambient temperatures may potentiate typical stimulant effects for the drugs lacking the 3,4-methylenedioxy ring, but may potentiate the behaviorally toxic/adverse effects for the drugs containing a 3,4-methylenedioxy ring. Thus, preclinical abuse liability studies conducted at standard laboratory temperatures may not fully capture the effects of psychostimulants and highlight the need to model the environments in which drugs are typically used by humans.