SCH 23390 inhibits the acquisition of nitrous oxide-induced conditioned place preference and the changes in ERK phosphorylation expression in nucleus accumbens of mice

Abstract

Nitrous oxide (N₂O) has a long history of abuse, but its abuse mechanism has not been clear yet. This research aimed at the possibility of mesolimbic dopaminergic system (MLDS) involved in the rewarding effect of N₂O. In this work, the rewarding behavior of N₂O in mice was evaluated using a typical gas-administered conditioned place preference (CPP) procedure. SCH 23390, a Dopamine D1 receptor (D1R) antagonist, and Haloperidol, a Dopamine D2 receptor (D2R) antagonist were administered during CPP to evaluate the role of dopamine receptors in the N₂O-induced CPP. The accompanying changes in phosphorylation of extracellular signal-regulated kinase (ERK) in MLDS related brain regions, including the ventral tegmental area (VTA), caudate putamen (CPu), prefrontal cortex (PFC), and nucleus accumbens (NAc) were measured to assess the neural plasticity changes in the CPP mice by Western blot analysis. Results revealed that 60% N₂O induced CPP in the gas-administered mice and promoted the ERK phosphorylation (p-ERK) in the NAc and CPu during the test session of the CPP test. Pretreatment of SCH 23390 (0.5 mg/kg) inhibited the acquisition of N₂O-induced CPP and the enhanced p-ERK in NAc. It suggested that Dopamine D1 receptor may play an important role in the acquisition of N₂O-induced CPP and the accompanied ERK activation in the NAc, which provide insight into the molecular mechanism in the rewarding properties of nitrous oxide.

Keywords: Conditioned place preference; Extracellular signal-regulated kinase; Mesolimbic dopaminergic system; Nitrous oxide; Nucleus accumbens.