Hippocampal neurogenesis interferes with extinction and reinstatement of methamphetamine-associated reward memory in mice

Neuropharmacology. 2021 Jul 14:108717. doi: 10.1016/j.neuropharm.2021.108717. Online ahead of print.ABSTRACTDrugs of abuse, including morphine and cocaine, can reduce hippocampal neurogenesis (HN). Whereas promotion of HN is being increasingly recognized as a promising strategy for treating morphine and cocaine addiction. The present study is focused on exploring the changes of HN during methamphetamine (METH) administration and further clarify if HN is involved in METH-associated reward memory. After successfully establishing the conditioned place preference (CPP) paradigm to simulate the METH-associated reward memory in C57BL/6 mice, we observed that HN was significantly inhibited during METH (2 mg/kg, i. p.) administration and returned to normal after the extinction of METH CPP, as indicated by the immunostaining of bromodeoxyuridine (BrdU) and doublecortin (DCX) in the hippocampus. To promote/inhibit HN levels, 7,8-dihydroxyflavone (DHF), a small tyrosine kinase receptor B (TrkB) agonist and temozolomide (TMZ), an alkylating agent, were administered intraperitoneally (i.p.), respectively. The data showed that either DHF (5 mg/kg, i. p.) or TMZ (25 mg/kg, i. p.) pre-treatment before METH administration could significantly prolong extinction and enhance reinstatement of the reward memory. Notably, DHF treatment after METH administration significantly facilitated extinction and inhibited METH reinstatement, while TMZ treatment resulted in opposite effects. The present study ...

Source: Neuropharmacology - July 17, 2021 Category: Drugs & Pharmacology Authors: Xiaohang Che Yijun Bai Jialing Cai Yueyang Liu Yuting Li Meixue Yin Tianyu Xu Chunfu Wu Jingyu Yang Source Type: research