Selective loss of dopaminergic neurons in the substantia nigra pars compacta after systemic administration of MPTP facilitates extinction learning

摘要: Abstract Aims Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc). In PD, thinking and retrieval deficits often arise from cognitive impairments. However, mechanism disorders PD remains unknown. Therefore, we investigated function model mice produced intraperitoneal administration 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which specifically destroys DAergic SNpc. Main methods We evaluated MPTP-treated (PD mice) using contextual fear conditioning test. test, each experiment consists three phases: training, re-exposure, testing. Mice were trained with foot shock (a weak unconditioned stimulus: 1 mA/2 s duration, once, or an intense 2 mA/2 s twice), 24 h later, re-exposed to training context for 3 min determine reconsolidation 30 min extinction. The percentage time spent freezing was measured during test session as indexes memory consolidation, reconsolidation, Key findings Reconsolidation occurred normally but extinction facilitated compared control mice. Moreover, retention attenuated earlier than controls following repeated conditioned stimuli every day. Significance selective SNpc showed retention, probably via learning.