cholecystokinin and Dyskinesia--Drug-Induced

Topics: Animals; Brain; Cholecystokinin; Dipeptides; Dopamine; Dyskinesia, Drug-Induced; Endorphins; Female; Humans; Morphine; Naloxone; Neuropeptides; Neurotensin; Neurotransmitter Agents; Peptides; Peptides, Cyclic; Rats; Substance P

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

In chronic alcohol abusers with no pancreatic disease, secretin was found to induce a paradoxical spasmodic response in the sphincter of Oddi (SO) instead of the relaxation observed in controls. Cerulein, on the contrary, had a normal relaxing effect on the SO.. We previously reported SO dyskinesia in cases of chronic pancreatitis. Here we investigated whether chronic alcohol consumption may have contributed to the genesis of this dyskinesia.. SO and main pancreatic duct pressures were recorded endoscopically with a dual electronic pressure sensor in 27 chronic alcohol abusers and compared with the values obtained in 15 normal controls. These pressures were recorded both in the basal state and after applying hormonal stimulation by injecting either secretin (1 CU/kg) or cerulein (75 ng/kg).. Cerulein relaxed the SO in both the controls and the chronic alcohol abusers, whereas it transiently enhanced the main pancreatic duct (MPD) pressure. Secretin induced a wave of MPD hyperpressure (+15.4 +/- 3.0 mm Hg) in both groups of subjects, but in the alcoholic group, instead of relaxing SO, it significantly enhanced the amplitude of phasic contractions (+32.6 +/- 8.4 mm Hg). The SO basal pressure was also paradoxically enhanced by secretin in the alcoholic patients (28.8 +/- 8.2 vs 10.1 +/- 2.4 mm Hg).

Topics: Alcoholism; Ceruletide; Cholecystokinin; Dyskinesia, Drug-Induced; Female; Humans; Male; Manometry; Middle Aged; Pancreatic Ducts; Reference Values; Secretin; Sphincter of Oddi