Behavioral and neurochemical changes induced by repetitive combined treatments of ketamine and amphetamine in mice
Journal
Neurochemical Research
Journal Volume
39
Journal Issue
11
Pages
2180-2188
Date Issued
2014
Author(s)
Abstract
The combined abuse of recreational drugs such as ketamine (Ket) and amphetamine (Amph) should be seriously considered important social and health issues. Numerous studies have documented the behavioral and neurochemical changes associated with polydrug administration; however, most studies have only examined the acute effects. The consequences following chronic repetitive polydrug use are less studied. In the present study, intraperitoneal injections of saline, Amph (5 mg/kg), low dose Ket (LK, 10 mg/kg), high dose Ket (HK, 50 mg/kg), or Amph plus LK or HK (ALK or AHK) were conducted twice a day for three consecutive days, and one final treatment was administered on day 4. After seven total treatments, animal behaviors, including locomotion, stereotypy and ataxia, were examined in a novel open field. The expression of GAD67 and dopamine (DA) levels were assessed in the striatum and motor-related cortices using immunohistochemistry and high-performance liquid chromatography. Drug-induced hyperactivities and Amph-mediated potentiation of Ket-triggered ataxia manifested after repeated drug treatments. A significant increase in the number of GAD67-positive puncta in the striatum and motor-related cortices was observed, suggesting a neural adaptive change in the GABAergic system. Four hours after the final treatment, while the behavioral hyperactivities had ceased, considerable changes were still evident in the motor-related cortices, suggesting modulation to the DAergic system. Together, our results show the interactive effects of these two drugs in behavioral and neurochemical aspects and neural adaptive changes in the GABAergic and DAergic systems. ? Springer Science+Business Media New York, 2014.
SDGs
Other Subjects
amphetamine; dopamine; glutamate decarboxylase 67; ketamine; sodium chloride; amphetamine; dopamine; ketamine; adult; animal behavior; animal experiment; animal model; animal tissue; Article; ataxia; behavior change; caudate nucleus; controlled study; corpus striatum; disease duration; dopaminergic system; experimental hyperactivity; exploratory behavior; GABAergic system; immunohistochemistry; locomotion; male; mobilization; motor cortex; mouse; multiple drug abuse; neurochemistry; nonhuman; nucleus accumbens; open field test; putamen; repeated drug dose; reversed phase high performance liquid chromatography; somatosensory cortex; stereotypy; upregulation; young adult; animal; animal behavior; brain; drug combination; drug effects; metabolism; motor activity; procedures; Amphetamine; Animals; Behavior, Animal; Brain; Dopamine; Drug Therapy, Combination; Ketamine; Male; Mice; Motor Activity; Stereotyped Behavior
Publisher
Springer New York LLC
Type
journal article