Methamphetamine (METH) relapse affects the function of the serotonergic system, which this system important for synaptic plasticity and brain-derived neurotrophic factor (BDNF) level. While there is a clear distribution of serotonin receptors in the reward and memory areas but the function of 5-HT1D receptor isn't known. This article assessed effects of BRL15572 hydrochloride (5-HT1D receptor antagonist) on behavior, long-term potentiation (LTP), and BDNF level in reinstated METH-rats. Conditioned place preference was induced by injecting METH (5 mg/kg; i.p.) or saline on the conditioning days. On the last day of extinction, they received priming METH [simultaneously with BRL (2 μg/5 μl; i.c.v.) or vehicle] or saline or saline + vehicle. Preference scores, LTP components and expression of BDNF were measured on the following day. The preference score of METH treatment increased dramatically more than the sham group and co-administration of BRL + METH couldn't decrease the preference score than the METH group. Also, METH treatment increased the population spike relative to the sham group, whereas the treatment METH + BRL attenuated this parameter than METH group. Furthermore, BDNF expression significantly increased in the METH group although it decreased markedly upon treatment with BRL. These results suggest that future studies should evaluate the potential of 5-HT1D antagonist for METH-reinstatement behaviors.