کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5855061 | 1562057 | 2013 | 8 صفحه PDF | دانلود رایگان |
- Amphetamine exacerbated the ataxia behavior of mice induced by ketamine.
- Ketamine worsened locomotion and stereotypy of amphetamine-treated mice.
- Dopamine contents increased in the striatum, and motor and somatosensory cortices.
- Both drugs elicited the up-regulated striatal GAD67 mRNA and protein expression.
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 (5Â mg/kg), low Ket (LK, 10Â mg/kg), high Ket (HK, 50Â mg/kg), or Amph and LK or HK (ALK or AHK) and examined their behavioral and neurochemical changes at 0.5 and 2Â 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.
Journal: NeuroToxicology - Volume 37, July 2013, Pages 136-143