To investigate the behavioral and biomolecular similarity between neuralgia and depression, a trigeminal neuralgia (TN) mouse model was established by constriction of the infraorbital nerve (CION) to mimic clinical trigeminal neuropathic pain. A mouse learned helplessness (LH) model was developed to investigate inescapable foot-shock-induced psychiatric disorders like depression in humans. Mass spectrometry was used to assess changes in the biomolecules and signaling pathways in the hippocampus from TN or LH mice. TN mice developed not only significant mechanical allodynia but also depressive-like behaviors (mainly behavioral despair) at 2 weeks after CION, similar to LH mice. MS analysis demonstrated common and distinctive protein changes in the hippocampus between groups. Many protein function families (such as cell-to-cell signaling and interaction, and cell assembly and organization,) and signaling pathways (e.g., the Huntington's disease pathway) were involved in chronic neuralgia and depression. Together, these results demonstrated that the LH and TN models both develop depressive-like behaviors, and revealed the involvement of many psychiatric disorder-related biomolecules/pathways in the pathogenesis of TN and LH.
Animals ; Avoidance Learning ; physiology ; Brain-Derived Neurotrophic Factor ; metabolism ; Depression ; etiology ; pathology ; Disease Models, Animal ; Electroshock ; adverse effects ; Functional Laterality ; Helplessness, Learned ; Hindlimb Suspension ; psychology ; Hippocampus ; metabolism ; Male ; Mass Spectrometry ; Mice ; Mice, Inbred C57BL ; Orbit ; innervation ; Pain Measurement ; Proteomics ; methods ; Reaction Time ; physiology ; Signal Transduction ; physiology ; Trigeminal Neuralgia ; etiology ; pathology

OBJECTIVETo explore the possible neurophysiologic mechanisms of propofol and N-methyl-D- aspartate (NMDA) receptor antagonist against learning-memory impairment of depressed rats without olfactory bulbs.

METHODSModels of depressed rats without olfactory bulbs were established. For the factorial design in analysis of variance, two intervention factors were included: electroconvulsive shock groups (with and without a course of electroconvulsive shock) and drug intervention groups [intraperotoneal (ip) injection of saline, NMDA receptor antagonist MK-801 and propofol. A total of 60 adult depressed rats without olfactory bulbs were randomly divided into 6 experimental groups (n=10 per group): ip injection of 5 ml saline; ip injection of 5 ml of 10 mg/kg MK-801; ip injection of 5 ml of 10 mg/kg MK-801 and a course of electroconvulsive shock; ip injection of 5 ml of 200 mg/kg propofol; ip injection of 5 ml of 200 mg/kg propofol and a course of electroconvulsive shock; and ip injection of 5 ml saline and a course of electroconvulsive shock. The learning-memory abilities of the rats was evaluated by the Morris water maze test. The content of glutamic acid in the hippocampus was detected by high-performance liquid chromatography. The expressions of p-AT8Ser202 in the hippocampus were determined by Western blot analysis.

RESULTSPropofol, MK-801 or electroconvulsive shock alone induced learning-memory impairment in depressed rats, as proven by extended evasive latency time and shortened space probe time. Glutamic acid content in the hippocampus of depressed rats was significantly up-regulated by electroconvulsive shock and down-regulated by propofol, but MK-801 had no significant effect on glutamic acid content. Levels of phosphorylated Tau protein p-AT8Ser202 in the hippocampus was up-regulated by electroconvulsive shock but was reduced by propofol and MK-801 alone. Propofol prevented learning-memory impairment and reduced glutamic acid content and p-AT8Ser202 levels induced by electroconvulsive shock.

CONCLUSIONElectroconvulsive shock might reduce learning-memory impairment caused by protein Tau hyperphosphorylation in depressed rats by down-regulating glutamate content.

Animals ; Depression ; psychology ; Dizocilpine Maleate ; pharmacology ; Electroshock ; Glutamic Acid ; analysis ; Learning Disorders ; prevention & control ; Male ; Memory Disorders ; prevention & control ; Phosphorylation ; Propofol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; tau Proteins ; metabolism

The purpose of the present study is to explore the relationship of spatial learning ability and specific electrical activities of neural oscillations in the rat. The fast and general avoidance response groups were selected on the basis of the animals' responses to the electric shock in Y type maze, and their local field potentials (LFPs) of hippocampal CA3 area were recorded by wireless telemetry before and after shock avoidance training, respectively. The components of neural oscillations related to spatial identifying and learning ability were analyzed. The results showed that, compared with the general avoidance response group, the fast avoidance response group did not show any differences of LFPs in hippocampal CA3 area before electric shock avoidance trial, but showed significantly increased percentages of 0-10 Hz and 30-40 Hz rhythm in right hippocampal CA3 area after the shock avoidance training (P < 0.01 or P < 0.05). Fast Fourier transform showed that percentage increase of 0-10 Hz band occurred mainly in θ (3-7 Hz) frequency, and 30-40 Hz frequency change was equivalent to the γ1 band. Furthermore, compared with those before training, only the percentages of β, β2 (20-30 Hz) and γ1 rhythm increased (P < 0.01 or P < 0.05) in fast avoidance response rats after training, while the θ rhythm percentage remained unchanged. In contrast, θ rhythm percentage and the large amplitude (intensity: +2.5 - -2.5 db) θ waves in right CA3 area of general avoidance response rats were significantly reduced after training (P < 0.01). These results suggest that the increased percentages of β2 and γ1 rhythm and high-level (unchanged) percentage of θ rhythm in the right hippocampus CA3 area might be related to strong spatial cognition ability of fast avoidance response rats.
Animals ; Avoidance Learning ; Beta Rhythm ; CA3 Region, Hippocampal ; physiology ; Electroshock ; Gamma Rhythm ; Rats ; Spatial Learning ; Theta Rhythm

OBJECTIVETo explore and compare the effects of propofol, ginsenoside Rg-1, protein phosphatae-2A, and lithium on the learning and memory and the concentration of glutamic acid in hippocampus after the electroconvulsive therapy (ECT) in the model of depressed rats induced after the removal of olfactory bulb.

METHODSThe depressed rats were randomized into ECT intervention (two levels:no disposition and a course of electroconvulsive shock) and drug intervention (five levels:microinjection of saline injection, propofol, ginsenoside Rg-1, protein phosphatae-2A, and lithium, 20 g/L). Learning and memory were evaluated using the Morris water maze test within 24 h after the course of ECT. Glutamate contents in the hippocampus of rats were examined using high-performance liquid chromatography.

RESULTSBoth propofol alone and ECT alone induced the impairment of learning and memory in depressed rats, but their combination alleviated the such impairment caused by ECT. Ginsenoside Rg-1, protein phosphatae-2A ,and lithium had no obvious effect on the leaning and improved the learning and memory when in combination with ECT. There was a synergic effect between ECT intervention and drug intervention. ECT remarkably increased the glutamate content in the hippocampus of depressed rats, which could be reduced by both propofol and ginsenoside Rg-1. Protein phosphatae-2A and lithium did not affect glutamate content in the hippocampus of depressed rats before and after ECT.

CONCLUSIONSECT can increase the content of glutamate in hippocampus and thus cause the impairment of learning and memory in depressed rats. Propofol and ginsenoside Rg-1 can ameliorate the impairment by reducing the content of glutamate in hippocampus. Protein phosphatae-2A and lithium may also improve the learning and memory in depressed rats.

Animals ; Electroshock ; Ginsenosides ; pharmacology ; Glutamic Acid ; metabolism ; Hippocampus ; metabolism ; Lithium ; pharmacology ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Propofol ; pharmacology ; Protein Phosphatase 2 ; pharmacology ; Rats ; Rats, Sprague-Dawley

Electroconvulsive shock (ECS) induces not only an antidepressant effect but also adverse effects such as amnesia. One potential mechanism underlying both the antidepressant and amnesia effect of ECS may involve the regulation of serotonin (5-hydroxytryptamine) 6 (5-HT6) receptor, but less is known about the effects of acute ECS on the changes in 5-HT6 receptor expression in the hippocampus. In addition, as regulation of 5-HT receptor expression is influenced by the number of ECS treatment and by interval between ECS treatment and sacrifice, it is probable that magnitude and time-dependent changes in 5-HT6 receptor expression could be influenced by repeated ECS exposure. To explore this possibility, we observed and compared the changes of 5-HT6 receptor immunoreactivity (5-HT6 IR) in rat hippocampus at 1, 8, 24, or 72 h after the treatment with either a single ECS (acute ECS) or daily ECS for 10 days (chronic ECS). We found that acute ECS increased 5-HT6 IR in the CA1, CA3, and granule cell layer of hippocampus, reaching peak levels at 8 h and returning to basal levels 72 h later. The magnitude and time-dependent changes in 5-HT6 IR observed after acute ECS were not affected by chronic ECS. These results demonstrate that both acute and chronic ECS transiently increase the 5-HT6 IR in rat hippocampus, and suggest that the magnitude and time-dependent changes in 5-HT6 IR in the hippocampus appear not to be influenced by repeated ECS treatment.
Amnesia ; Animals ; Electroshock* ; Hippocampus* ; Rats* ; Serotonin

This study explored the effect of the excitatory amino acid receptor antagonists on the impairment of learning-memory and the hyperphosphorylation of Tau protein induced by electroconvulsive shock (ECT) in depressed rats, in order to provide experimental evidence for the study on neuropsychological mechanisms improving learning and memory impairment and the clinical intervention treatment. The analysis of variance of factorial design set up two intervention factors which were the electroconvulsive shock (two level: no disposition; a course of ECT) and the excitatory amino acid receptor antagonists (three level: iv saline; iv NMDA receptor antagonist MK-801; iv AMPA receptor antagonist DNQX). Forty-eight adult Wistar-Kyoto (WKY) rats (an animal model for depressive behavior) were randomly divided into six experimental groups (n = 8 in each group): saline (iv 2 mL saline through the tail veins of WKY rats ); MK-801 (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats) ; DNQX (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats ); saline + ECT (iv 2 mL saline through the tail veins of WKY rats and giving a course of ECT); MK-801 + ECT (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats and giving a course of ECT); DNQX + ECT (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats and giving a course of ECT). The Morris water maze test started within 1 day after the finish of the course of ECT to evaluate learning and memory. The hippocampus was removed from rats within 1 day after the finish of Morris water maze test. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. The contents of Tau protein which included Tau5 (total Tau protein), p-PHF1(Ser396/404), p-AT8(Ser199/202) and p-12E8(Ser262) in the hippocampus of rats were detected by immunohistochemistry staining (SP) and Western blot. The results showed that ECT and the glutamate ionic receptor blockers (NMDA receptor antagonist MK-801 and AMPA receptor antagonist DNQX) induced the impairment of learning and memory in depressed rats with extended evasive latency time and shortened space exploration time. And the two factors presented a subtractive effect. ECT significantly up-regulated the content of glutamate in the hippocampus of depressed rats which were not affected by the glutamate ionic receptor blockers. ECT and the glutamate ionic receptor blockers did not affect the total Tau protein in the hippocampus of rats. ECT up-regulated the hyperphosphorylation of Tau protein in the hippocampus of depressed rats, while the glutamate ionic receptor blockers down-regulated it, and combination of the two factors presented a subtractive effect. Our results indicate that ECT up-regulates the content of glutamate in the hippocampus of depressed rats, which up-regulates the hyperphosphorylation of Tau protein resulting in the impairment of learning and memory in depressed rats.
Animals ; Disease Models, Animal ; Dizocilpine Maleate ; pharmacology ; Electroshock ; adverse effects ; Excitatory Amino Acid Antagonists ; pharmacology ; Glutamic Acid ; metabolism ; Hippocampus ; metabolism ; Learning ; Memory ; Memory Disorders ; Phosphorylation ; Quinoxalines ; pharmacology ; Rats ; Rats, Inbred WKY ; Rats, Sprague-Dawley ; Receptors, AMPA ; antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate ; antagonists & inhibitors ; tau Proteins ; metabolism

OBJECTIVETo explore the effect of the electroconvulsive shock (ECS) on the glutamate level and the hyperphosphorylation of tau protein in depressed rats.

METHODSThe depression rat models whose olfactory bulbs were removed were established. Using the analysis of variance of factorial design, we set up two intervention factors including electric current (three levels: 25, 50, and 75 mA) and duration (three levels: 3, 6, and 9 times), which constituted 9 combinations (n=6). Fifty-four adult depression rat models whose olfactory bulbs were removed were randomly divided into nine experimental groups (n=6 in each group). The hippocampus was removed within 12 hours after the ECS finished. The level of glutamate in the hippocampus was detected by high-performance liquid chromatography, and that of Tau protein, which includes p-PHF-1(Ser396/404), p-AT8(Ser199/202), and p-12E8(Ser262), in the hippocampus with Western blot analysis.

RESULTSThe glutamate level and the hyperphosphorylation of tau protein in the hippocampus of depressed rats remarkably increased. The changes of the hyperphosphorylation of tau protein were correlated with the electric current and duration of ECS, and these two factors showed an synergic effect.

CONCLUSIONECS enhances the hyperphosphorylation of tau protein in the hippocampus of depressed rats by up-regulating the glutamate level.

Animals ; Depressive Disorder ; metabolism ; Disease Models, Animal ; Electroshock ; Glutamic Acid ; metabolism ; Hippocampus ; drug effects ; metabolism ; Male ; Olfactory Bulb ; surgery ; Phosphorylation ; drug effects ; Rats ; Rats, Sprague-Dawley ; tau Proteins ; metabolism

INTRODUCTIONThe need for the rational development of newer and adjuvant drugs to treat epilepsy has prompted this study of the potential anticonvulsant effect of amlodipine.

METHODSThe acute effect was studied in mice in single doses of 1 mg/kg, 2 mg/kg and 4 mg/kg of amlodipine and the chronic effect was studied in doses of 1 mg/kg and 4 mg/kg (administered daily for 21 days) using the maximal electroshock seizure and pentylenetetrazole-induced seizure models of epilepsy. Sodium valproate and normal saline were used as the standard and control, respectively.

RESULTSFor the acute study, in the maximal electroshock seizure model, the administration of 1 mg/kg of amlodipine resulted in the complete abolition of seizures in 33 percent of the mice, and this was increased to 67 percent with the administration of 4 mg/kg. In the pentylenetetrazole-induced seizure model, the administration of 1 mg/kg and 2 mg/kg amlodipine protected 33 percent of the animals from mortality, and 67 percent were protected with the administration of 4 mg/kg. For the chronic study, in the maximal electroshock seizure model, the administration of 1 mg/kg amlodipine resulted in the complete abolition of seizures in 40 percent of the mice and in 60 percent, with the administration of 4 mg/kg. In the pentylenetetrazole-induced seizure model, 50 percent of the mice were protected from mortality with 1 mg/kg amlodipine and 60 percent, with 4 mg/kg amlodipine.

CONCLUSIONThese findings indicate that amlodipine may be a good candidate as an add-on therapy for epilepsy.

Amlodipine ; therapeutic use ; Animals ; Anticonvulsants ; therapeutic use ; Calcium Channel Blockers ; therapeutic use ; Convulsants ; toxicity ; Disease Models, Animal ; Electroshock ; adverse effects ; Female ; Male ; Mice ; Mice, Inbred Strains ; Pentylenetetrazole ; toxicity ; Seizures ; drug therapy ; etiology ; prevention & control ; Time Factors ; Valproic Acid ; therapeutic use

OBJECTIVE: The interaction between MK-801, a model of psychosis and KCl-induced depolarization or electroconvulsive shock (ECS), a therapeutic model of electroconvulsive therapy (ECT), was investigated in SH-SY5Y cells and the rat frontal cortex. METHODS: SH-SY5Y cells were pretreated with 1 microM MK-801 for 15 min, followed by cotreatment with 100 mM KCl for 5 min. MK-801 was reintroduced after the KCl was washed out, and the samples were incubated before harvesting. For the experiments in rats, male Sprague-Dawley rats were treated with MK-801 followed by ECS. Immunoblot analyses of glycogen synthase kinase 3beta (GSK3beta) (Ser9), AKT (Ser473) and extracellular legulated kinase (ERK)1/2 in SH-SY5Y cells and the rat frontal cortex were performed. RESULTS: KCl-induced neuronal depolarization resulted in the transient dephosphorylation of AKT (Ser473) and GSK3beta (Ser9), followed by increased phosphorylation of the enzymes in SH-SY5Y cells. Cotreatment with MK-801 and KCl inhibited the initial dephosphorylation of AKT and GSK3beta produced by KCl-induced neuronal depolarization. Similarly, ECS resulted in the transient dephosphorylation of AKT (Ser473) and GSK3beta (Ser9), whereas cotreatment with MK-801 inhibited the initial dephosphorylation of AKT (Ser473) and GSK3beta (Ser9) produced by ECS in the rat frontal cortex. No significant interaction was observed between MK-801 and KCl in the dephosphorylation of ERK1/2. CONCLUSION: These results suggest that an antagonistic interplay between MK-801 and neuronal depolarization by KCl or ECS is involved the regulation of AKT (Ser473) and GSK3beta (Ser9) phosphorylation.
Animals ; Dizocilpine Maleate* ; Electroconvulsive Therapy ; Electroshock ; Glycogen Synthase Kinases ; Humans ; Male ; Neurons* ; Phosphorylation ; Phosphotransferases ; Psychotic Disorders ; Rats* ; Rats, Sprague-Dawley

OBJECTIVETo investigate effects of acute maximal electroshock (MES) and chronic transauricular kindled seizures on learning abilities in Sprague-Dawley rats.

METHODSAn acute MES was induced by giving an alternating current (150 mA, 0.2 s) through ear-clip electrodes. Chronic transauricular kindled seizure was induced by repeated application of initially subconvulsive electrical stimulation (40 mA, 0.2 s) through ear-clip electrodes once every 24 h. An 8-arm radial maze (4 arms baited) was used to measure learning abilities. Histamine, glutamate and gamma-aminobutyric acid (GABA) were measured by high-performance liquid chromatography (HPLC).

RESULTIn the acquisition learning process, an acute MES increased reference memory errors but not working memory errors. In addition, it increased GABA levels in the hippocampus. On the other hand, chronic transauricular kindled seizures increased both working and reference memory errors in retrieval memory process, and this lasted for at least 3 weeks. Chronic transauricular kindled seizures induced CA1 neuron damage and a decrease in histamine levels in the hippocampus.

CONCLUSIONDifferent types of kindling seizure produce different effects on cognitive behavior: (1) an acute MES impairs learning ability, which may be associated with an abnormal plasticity and an increase of GABA in the hippocampus; (2) the chronic transauricular kindled seizure impairs retrieval memory mainly, which may be related to CA1 neuron damage and a decrease in histaminergic activity in the hippocampus.

Animals ; Chronic Disease ; Electric Stimulation ; instrumentation ; methods ; Electrodes ; Electroshock ; adverse effects ; Hippocampus ; metabolism ; Histamine ; metabolism ; Kindling, Neurologic ; physiology ; Learning Disorders ; etiology ; metabolism ; physiopathology ; Maze Learning ; physiology ; Memory Disorders ; etiology ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Seizures ; complications ; physiopathology ; gamma-Aminobutyric Acid ; metabolism