How the histamine N-methyltransferase inhibitor metoprine alleviates methamphetamine reward

Several agents that activate brain histaminergic neurotransmission have been reported to improve methamphetamine (METH)-induced behavioral aberrations. In this review, we present research demonstrating that pretreatment with metoprine, a selective inhibitor of histamine N-methyltransferase (HMT), attenuates the reinforcing effects of METH in mice. Pretreatment with metoprine decreased METH-induced reinforcement as evaluated in the conditioned place preference (CPP) test. Metoprine pretreatment alone produced an increase in the CPP score with the same score level as that observed in mice treated with METH plus metoprine. No changes in alternation behaviors or numbers of marbles buried were observed in metoprine-treated mice measured in the Y-maze test and in the marble burying test, respectively. The locomotor activity was augmented after metoprine administration. These observations suggest that metoprine alleviates METH-induced rewarding property and hyperlocomotion. Metoprine is likely to augment spontaneous locomotor activities without mood alterations or short-term memory impairment. Brain histaminergic system is a new hope for treatment of METH dependence. Review Article How the histamine N-methyltransferase inhibitor metoprine alleviates methamphetamine reward Nobue Kitanaka1, Junichi Kitanaka1*, F Scott Hall2, Satoshi Okumura1#, Tomoyuki Sakamoto1#, George R Uhl3 and Motohiko Takemura1 1Department of Pharmacology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan 2Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA 3Offi ce of Research & Development, New Mexico VA Healthcare System/BRINM, Albuquerque, NM, USA #These authors contributed equally to this study as medical students participating in an orientation course for medical sciences (2014) held in the Department of Pharmacology, Hyogo College of Medicine Dates: Received: 02 May, 2017; Accepted: 11 May, 2017; Published: 12 May, 2017 *Corresponding author: Junichi Kitanaka, Department of Pharmacology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan, Tel: 81798456333; Fax: 81798456332; E-mail: