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Hippocampal neurogenesis interferes with extinction and reinstatement of methamphetamine-associated reward memory in mice
- Source :
- Neuropharmacology. 196:108717
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Drugs 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 indicated that METH administration could induce a temporal inhibitory effect on HN. More importantly, promotion of HN after the acquisition of METH-associated reward memory, but not inhibition of HN or promotion of HN before the acquisition of reward memory, could facilitate METH extinction and inhibit METH reinstatement, indicating the beneficial effect of HN on METH addiction by erasing the according reward memory.
- Subjects :
- Agonist
medicine.drug_class
Neurogenesis
Amphetamine-Related Disorders
Conditioning, Classical
Hippocampus
Tropomyosin receptor kinase B
Pharmacology
Extinction, Psychological
Methamphetamine
Mice
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Reward
Memory
Temozolomide
medicine
Animals
biology
business.industry
Meth
Extinction (psychology)
Flavones
Conditioned place preference
Doublecortin
Mice, Inbred C57BL
chemistry
biology.protein
Central Nervous System Stimulants
business
medicine.drug
Subjects
Details
- ISSN :
- 00283908
- Volume :
- 196
- Database :
- OpenAIRE
- Journal :
- Neuropharmacology
- Accession number :
- edsair.doi.dedup.....3788463b636a0969cb17941f74039e27