No abstract available.
Dizocilpine Maleate* ; Dopamine* ; Methamphetamine*

No abstract available.
Animals ; Dizocilpine Maleate* ; Rats* ; Spinal Cord*

Tardive dyskinesia(TD) is a serious side effect of long-term treatment with neuroleptic medications. To investigate if glutamatergic hyperfunction is associated with TD, effect of MK-801 on the prevention and treatment of TD was studied using a rat model, i.e., vacuous chewing movements(VCM). When comparing VCM scores of Group I(haldol decanoate+MK-801) with that of Group II(hadol decanoate+phosphate buffer saline), late measured VCM scores of former were significantly lower than that of latter, meaning that MK-801 is effective in the prevention of VCM. Furthermore, when MK-801 is also effective in the treatment of VCM. From the above results, it is suggested that glutamatergic hyperfunction might be involved in the development of TD and MK801 could be effective in the prevention and treatment of it.
Dizocilpine Maleate* ; Mastication ; Models, Animal ; Movement Disorders*

No abstract available.
6-Cyano-7-nitroquinoxaline-2,3-dione* ; Cycloheximide* ; Dizocilpine Maleate*

BACKGROUND: There has been much interest in the involvement of wind-up in the hyperalgesia and allodynia of chronic pain syndrome. To investigate the behavioral parallels of this wind-up phenomenon, we evaluated the effects of intrathecal morphine, clonidine and MK801 on the formalin test in the rats. METHOD: All experimental animals were divided randomly into six groups. In group 1(n=7), normal saline 50 l was administered through the intrathecal catheter(PE10, 8 cm in length). In group 2(n=7), morphine 10 g was administered through the catheter. In group 3(n=7), group 4(n=7), group 5(n=7) and group 6(n=7), clonidine 10 g, clonidine 20 g, MK801 1 g, MK801 10 g was administered in same manner, respectively. Thirty min after recoverying from anesthesia, 50 l 5% formalin was injected in the hind paw. To quantify the formalin response, we counted the number of spontaneous flinching for 60 min. RESULT: Intrathecal morphine(group 2) decreased the number of paw flinches in both phases 1 and 2 readily compared to control(p<0.05). In the clonidine(group 3 and 4), both groups decreased the number of flinching in both phases 1 and 2, but there was no significant difference between two groups. In group 5, intrathecal MK-801 decreased the number of paw flinches in phase 2. In group 6, intrathecal MK-801 decreased the number of paw flinches in both phases 1 and 2. CONCLUSION: This study suggest that wind-up is readily blocked by pretreatment of morphine, clonidine and MK801.
Analgesics ; Anesthesia ; Animals ; Catheters ; Chronic Pain ; Clonidine* ; Dizocilpine Maleate* ; Formaldehyde* ; Hyperalgesia ; Morphine* ; Pain Measurement* ; Rats*

OBJECTIVE: Early maternal separation (EMS) during the development has been known to influence the alteration of behavior in adulthood. Nitric oxide (NO) may have been implicated to play a crucial role in the neurodevelopment as an intracellular and intercellular messenger. This study was designed to investigate the neurochemical mechanism of the behavioral changes resulting from EMS during the development in juvenile rats. METHODS: Experimental group consisted of subjects that were removed and weaned from the day on postnatal day 15. Control group were the litters that experienced no EMS until postnatal day 21. On postnatal day 15 and 36, the locomotor activity (LA) was measured. On postnatal day 36 the behavioral changes in the forced swimming test (FST) were also measured. Test drugs were intraperitoneally injected including MK-801 (0.5 mg/kg), N omega-nitro-L-arginine (L-NA, 20 mg/kg), paroxetine (20 mg/kg), and bupropion (150 mg/kg). RESULTS:EMS produced the decrease of LA significantly in juvenile rats (p<0.001). Both MK-801 and L-NA increased LA in experimental group (p<0.001) and control group (p<0.05). The degree of increase was higher in experimental group than in control group. However, both paroxetine and bupropion increased LA in experimental group (p<0.001, p<0.05), but not in control group. In the FST, immobility was significantly increased in experimental group compared with control group (p<0.001). The increases of immobility in experimental group were abolished after injecting MK-801, L-NA, paroxetine, and bupropion, respectively. CONCLUSION: These results indicate that EMS during the development can lead to behavioral abnormalities in juvenile rats. The underlying neurochemical mechanism of this behavioral changes may be, in part, related to the glutamatergic NMDA-NO pathway. This suggests that glutamatergic NMDA-NO pathway vulnerable to stress may predispose to depression.
Animals ; Bupropion ; Depression ; Dizocilpine Maleate ; Motor Activity ; Nitric Oxide ; Nitroarginine ; Paroxetine ; Rats ; Swimming

The anti-allodynic effect of NMDA receptor antagonist and acupuncture treatments were explored through spinal p35 regulation of diabetic neuropathic rat. We evaluated the change over time of p35/p25 protein levels in the spinal cord compared with behavioral responses to thermal and mechanical stimulation in streptozotocin (STZ)-induced diabetic rats. Additionally, we studied p35 expression when electroacupuncture (EA) and a sub-effective dose of NMDA (N-methyl-D-aspartate) receptor antagonist (MK-801) were used to treat hyperalgesia in the diabetic neuropathic pain (DNP). Thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT) were significantly decreased in the early stage of diabetes in rats. p35 expression after STZ injection gradually decreased from 1 week to 4 weeks compared to normal controls. p25 expression in 4-week diabetic rats was significantly higher than that of 2-week diabetic rats, and thermal PWL in 4-week diabetic rats showed delayed responses to painful thermal stimulation compared with those at 2 weeks. EA applied to the SP-9 point (2 Hz frequency) significantly prevented the thermal and mechanical hyperalgesia in the DNP rat. Additionally, EA combined with MK-801 prolonged anti-hyperalgesia, increased p35 expression, and decreased the cleavage of p35 to p25 during diabetic neuropathic pain. In this study we show EA combined with a sub-effective dose of MK-801 treatment in DNP induced by STZ that is related to p35/p25 expression in spinal cord.
Acupuncture ; Animals ; Diabetic Neuropathies ; Dizocilpine Maleate ; Electroacupuncture ; Hyperalgesia ; N-Methylaspartate ; Neuralgia ; Rats ; Spinal Cord ; Streptozocin

The effects of NMDA-receptor antagonist (MK-801) were assessed for the oxygen free radical mediated brain (hippocampus) injury with eighty rats which were exposed to carbon monoxide (CO) followed by hyperbaric oxygen (HBO) treatment. Superoxide dismutase (SOD) and malondialdehyde (MDA) were used as parameters of the oxygen free radical reaction. Experimental groups consisted of (1) control group (=breathing with air), (2) CO group (=exposed to CO after air breath), (3) CO-air group(exposed to CO after air breath followed by air breath), and (4) CO-HBO group (=exposed to CO after air breath followed by 3 ATA HBO). Each group was divided two subgroup according to the pretreatment (normal saline or MK-801). CO, CO-air and HBO groups increased in SOD activity as compared with control group. And CO-air and HBO groups increased in MDA as compared with control and CO group. Pretreatment of MK-801 decreased SOD activities significantly (p-value<.05) , but MDA amount not significantly (p-value=.107). These results suggest a useful protective effect of NMDA-receptor antagonist (MK-801) in CO induced hippocampal injury mediated by oxygen free radicals.
Animals ; Brain Injuries* ; Brain* ; Carbon Monoxide ; Dizocilpine Maleate ; Free Radicals ; Malondialdehyde ; Oxygen* ; Rats* ; Superoxide Dismutase

Despite some innate limitations, animal models are a potent investigative tool when used to model specific symptoms of a disorder. For example, MK-801, an N-methyl-D-aspartate receptor antagonist, is used as a pharmacological tool to induce symptoms found in some neuropsychiatric disorders. However, a close examination of literature suggests that the application window of MK-801 doses is relatively narrow between individual behavioral paradigms, necessitating careful characterization of the evoked behavioral aberrations and the doses used to induce them. Moreover, variation in behaviors depending on the animal strain, gender of the subject, and the timing of administration is observed, making it difficult to compare the behavioral characteristics reported in different studies. We aim to characterize the behavioral aberrations induced by different doses of MK-801 in CD-1 mice and create a ready reference for future studies. We used CD-1 mice to recapitulate behavioral impairments resulting from acute administration of MK-801. In 0.1 mg kg⁻¹, we observed diminished spontaneous alteration during the Y-maze test, while 0.12 mg kg⁻¹ resulted in hyperlocomotion and social deficit. Mice treated with 0.2 and 0.3 mg kg⁻¹ of MK-801 demonstrated a decreased self-grooming. Finally, all doses significantly impaired cliff avoidance behaviors suggesting increased impulsivity. These results affirm that MK-801 can effectively model various symptoms of different neuropsychiatric disorders in a dose-dependent manner. The observed sensitivity against spatial-memory impairment and impulsive behaviors at low concentration of MK-801 suggest that MK801 may modulate cognitive function and impulsivity in even lower concentration before it can modulate other behavioral domains.
Animals ; Avoidance Learning ; Cognition ; Dizocilpine Maleate ; Impulsive Behavior ; Mice ; Models, Animal ; N-Methylaspartate

BACKGROUND AND OBJECTIVES The temporal changes and the role of glutamate receptors in the recovery of vestibulogastrointestinal symptoms following unilateral labyrinthectomy (UL) were investigated in this study. Vestibulogastrointestinal symptoms were evaluated in terms of gastric emptying and intestinal transit. MATERIALS AND METHODS Expression of the c-Fos protein was observed in the solitary tract nucleus (STN) and rostral ventrolateral medullary nucleus (RVLM). These were measured at 0.5, 2, 6 and 24 h following UL in rats. RESULTS Gastric emptying and intestinal transit were significantly decreased for 6 h post UL and recovered to control levels within 24 h. Pretreatment of UL animals with MK-801 significantly increased the gastric emptying and intestinal transit. Bilateral labyrinthectomy significantly decreased the gastric emptying and intestinal transit compared to the intact labyrinthine animals but significantly increased when compared to UL animals. The expression of c-Fos protein was significantly increased in STN and RVLM compared to the control animals for 6 h post UL and recovered to control levels within 24 h. The expression was significantly decreased in animals that were pretreated with MK-801. CONCLUSION These results suggest that UL decreases the gastrointestinal motility, which recovers to control levels within 24 h post UL. Glutamate plays an important role in the recovery of vestibulogastrointestinal symptoms following UL.
Animals ; Dizocilpine Maleate ; Gastric Emptying ; Gastrointestinal Motility ; Glutamic Acid ; Receptors, Glutamate ; Solitary Nucleus