Effective therapies for Methamphetamine (METH) induced stereotyped behavior are still being explored. It is unclear whether Neuropeptide S (NPS) is involved in the mechanism of METH-induced stereotyped behavior. In the contemporary behavioral study, pretreatment with NPS reduces stereotyped circling significantly, but didn't have any impact on the total incidence of stereotypy and stereotyped sniffing and biting induced by METH (10 mg/kg). When METH (10 mg/kg) was administered to rats, the level of NPS in the cerebrospinal fluid was not affected, but pretreatment with NPS reversed METH-induced glutamate release in the hippocampus and striatum. The findings suggest that NPS receptor system is likely to involve in the METH-overdose-induced behaviors. (c) 2020 Published by Elsevier Inc.