sincalide and Neurodegenerative-Diseases

We investigated whether pretreatment with the neuropeptide cholecystokinin-8 affected methamphetamine (METH)-induced behavioral changes and dopaminergic neurodegeneration in male C57/BL6 mice. CCK-8 pretreatment alone had no effect on locomotion and stereotypic behavior and could not induce behavioral sensitization; however, it attenuated, in a dose-dependent manner, hyperlocomotion and behavioral sensitization induced by a low dose of METH (1mg/kg). CCK-8 attenuated METH-induced stereotypic behavior at a dose of 3mg/kg but not at 10mg/kg. CCK-8 pretreatment attenuated METH (10mg/kg)-induced hyperthermia, the decrease of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the striatum, and TH in the substantia nigra. CCK-8 alone had no effect on rectal temperature, TH and DAT expression in the nigrostriatal region. In conclusion, our study demonstrated that pretreatment with CCK-8 inhibited changes typically induced by repeated exposure to METH, such as hyperlocomotion, behavioral sensitization, stereotypic behavior, and dopaminergic neurotoxicity. These findings make CCK-8 a potential therapeutic agent for the treatment of multiple symptoms associated with METH abuse.

Topics: Amphetamine-Related Disorders; Animals; Body Temperature; Cholecystokinin; Corpus Striatum; Dopamine Agents; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Male; Methamphetamine; Mice, Inbred C57BL; Motor Activity; Neurodegenerative Diseases; Neuroprotective Agents; Peptide Fragments; Random Allocation; Stereotyped Behavior; Substantia Nigra; Tyrosine 3-Monooxygenase