Effects of histamine H3 receptor ligands on the rewarding, stimulant and motor-impairing effects of ethanol in DBA/2J mice

Histamine H3 receptor (H3R) antagonists are currently being investigated for the possible therapeutic use in various cognitive deficits such as those in schizophrenia, attention deficit hyperactivity disorder and Alzheimer’s disease. Our previous studies suggest a role for H3Rs in ethanol-related behaviors in rat and mice. Here we have examined the role of different H3R ligands on the effects of ethanol in conditioned place preference (CPP) paradigm, stimulation of locomotor activity and motor impairment in rotarod and balance beam in male DBA/2J mice. We found that H3R antagonists ciproxifan and JNJ-10181457 inhibited the ethanol-evoked CPP whereas H3R agonist immepip did not alter ethanol-induced place preference. Acute stimulatory response by ethanol was also modulated by H3R ligands. Ciproxifan increased ethanol activation when ethanol was given 1 g/kg but not at 1.5 g/kg dose. Immepip pretreatment diminished ethanol stimulation and increased motor-impairing effects of ethanol on the balance beam. In conclusion, these findings give further evidence of the involvement of H3R in the regulation of the effects of ethanol. The inhibition of ethanol reward by H3R antagonism implies that H3R might be a possible target to suppress compulsory ethanol seeking.This article is part of a Special Issue entitled ‘Trends in Neuropharmacology: In Memory of Erminio Costa’.