Inhalant self-administration of methamphetamine: The most similar model to human methamphetamine addiction

Abstract

Background: Methamphetamine (meth) is recognized as a highly addictive psychostimulant. Currently, there are no available treatments for meth abuse, and no animal model of meth self-administration has been proposed to represent human meth selfadministration. Objectives: We aimed to develop a model to study meth self-administration through inhalation in rats. Methods: Rats were placed in an inhaler apparatus (designed specifically for this purpose) for 15 min per day over two weeks. There were two levers in the cage. Pressing the passive lever had no outcomes. Whereas, for each active lever pressing, an infusion pump delivered 50 μL of meth or distilled water within two seconds. Meth was evaporated on a hot plate adjacent to the rat cage. After loading the drug over the hot plate, the blower fan was run, and the vaporized drug was blown by the fan into the rat cage. Then, meth-induced conditioned place preference and locomotor activity were assessed following 14 days of meth inhalation. The serum concentration of meth was also determined by gas chromatography-mass spectrometry. Results: In this model, the self-administration of meth through inhalation significantly increased locomotor activity, conditioned place preference, and plasma level of meth. Conclusions: We can conclude that the self-administration of meth through inhalation is a novel and effective route of selfadministration. Ournewprotocol presents a promising tool for examining drug-seeking/taking behaviorsandneural consequences in a noninvasive approach to reduce the stress of surgery and injection in laboratory animals and increase the validity of animal experiments.