title: Combinational effects of ketamine and amphetamine on behaviors and neurotransmitter systems of mice.
abstract: The combined ingestion of ketamine (Ket) and amphetamine (Amph) by drug-users has been rampant and produced more severe behavioral abnormality. However, the interactive consequences of the two drugs are still unclear. In this study, we treated adult male mice with a single i.p. injection of saline, Amph (5 mg/kg), low Ket (LK, 10 mg/kg), high Ket (HK, 50 mg/kg), or Amph and LK or HK (ALK or AHK) and examined their behavioral and neurochemical changes at 0.5 and 2 h post-injection. Compared with saline, Amph, LK or HK treatment alone increased the levels of motor activities such as locomotion, stereotypy or ataxia of mice. Notably, at combined treatments, LK and HK differentially exacerbated Amph-induced locomotion and stereotypy, whereas Amph worsened LK or HK-produced ataxia. The higher striatal dopamine levels of A, ALK and AHK groups correlated with their greater motor activities. The prolonged increase of dopamine in the motor cortex of ALK and AHK mice may associate with the longer duration of behavioral hyperactivity and greater peak score of locomotion; the greater dopamine level in the somatosensory cortex probably contributes to the more severe ataxia. Furthermore, in the striatum of all drug-treated groups, the expression of GAD67 mRNA and GAD67-positive punctates was higher than respective saline controls, indicating the involvement of GABAergic system in the drug-induced behavioral changes. Our results demonstrate the acute interplay between Amph and Ket in both behavioral and neurochemical aspects for the first time. Dopaminergic and GABAergic systems were affected differentially by the drugs in the striatum.
authors: Graduate Institute of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan.
authors: Chuan-Ching
authors: CC
authors: Lai
authors: Li-Jen
authors: LJ
authors: Lee
authors: Hsiang-Shu
authors: HS
authors: Yin
mesh_terms: D000661:Amphetamine / Q000633:toxicity*; D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D007649:Ketamine / Q000633:toxicity*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D007649:Ketamine; D000661:Amphetamine; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D004298:Dopamine