Effect of 5-HT1D Receptor Agonist on Hippocampal Long-Term Potentiation and Level of BDNF in Reinstated-Methamphetamine Rats

Methamphetamine (METH) is a psychostimulant that the precise mechanisms of its effects remain unknown and current relapsetreatments have low efficacy. However, brain-derived neurotrophic factor (BDNF) and neuronal plasticity are essential contributors, despite paradoxical reports and a lack of comprehensive studies. Serotonin is a key neuromodulator in this challenge. While there isa known distribution of 5-HT1D receptor in the reward and memory areas, the physiological function of this receptor is currently unknown. Here, we evaluated effect of a 5-HT1D receptor agonist (PNU142633) on the electrophysiology recording and level of BDNF.Materials and Methods: Rats were implanted with a cannula into lateral ventricle. After recovery, animals treated with saline or METH (5 mg/kg) during acquisition of conditioned place preference (CPP). On day 13 extinction, METH groups divided into four groups.They received METH (0: saline, 1, or 2.5 mg/kg; i.p.) +vehicle (5 μl/rat) or a priming dose of METH + PNU (2 μg/5 μL; i.c.v.) and conditioning scores were calculated on reinstatement day. Finally, electrophysiology and western blotting tests were performed for measurementsLTP components and expression of BDNF, respectively. Results: The results showed pre-treatment with PNU significantly reduced the reinstatement of priming METH seeking and level of BDNF expression was more than other groups. Furthermore, PS amplitude andEPSP slope in vehicle +priming METH rats were more than others. Also, PS amplitude in PNU+METH group was lower than priming METH group. Conclusions: These findings suggest that PNU can alter synaptic transmission and level of BDNF. Subsequently havetherapeutic potential for preventing METH relapse