Pitolisant Inhibits Alcohol Drinking and Improves Withdrawal Negative Affect Through Lateral Habenula Histaminergic Signaling in Mice.

ABSTRACT:

Background

Alcohol use disorder (AUD) is a chronic condition marked by compulsive drinking and withdrawal-related negative affect. Histamine (HA) signaling, particularly via the histamine H3 receptor (H3R), may modulate alcohol-related behaviors. We investigated the effects of pitolisant, an FDA-approved H3R antagonist, on ethanol (EtOH)-related behaviors in mice.

Method

Adult male C57BL/6J mice underwent acute or chronic (2 or > 8 weeks) intermittent alcohol exposure. Pitolisant pretreatment was administered, and then pharmacological behavior, histologic, and molecular assays were conducted.

Result

Pitolisant administration reduced acute EtOH-induced locomotor activation, conditioned place preference, and sedative effects, and also curtailed EtOH intake. It alleviate

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC12771655 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature