Anti-seizure effect and neuronal activity change in the genetic-epileptic model rat with acute and chronic vagus nerve stimulation.

Background: VNS showed time-dependent anti-seizure effect. However, the precise mechanism of VNS in acute and chronic anti-seizure effect has not been fully elucidated. Noda epileptic rat (NER) is genetic epilepsy model rat which exhibits spontaneous generalized tonic-clonic seizure (GTC) approximately once per 30 h and frequent dialeptic seizure (DS).

Serotonergic modulation of neuronal activity in the nucleus accumbens following repeated methamphetamine administration in rats.

Electrophysiological studies were performed to determine whether serotonergic modulation in the nucleus accumbens (NAcc) was affected after repeated methamphetamine (MAP) administration. NAcc slices (400 μm) from Wistar rats administered MAP (5 mg/kg) or saline once daily for 5 days were prepared 1, 5, or 10 days after the final injection. Population spikes (PS) induced by local stimulation of NAcc were recorded.

Inhibitory effects of levetiracetam on the high-voltage-activated L-type Ca²⁺ channels in hippocampal CA3 neurons of spontaneously epileptic rat (SER).

Levetiracetam (LEV) is a widely used antiepileptic agent for partial refractory epilepsy in humans. LEV has unique antiepileptic effects in that it does not inhibit electroshock- or pentylenetetrazol-induced convulsion, but does inhibit seizures in kindling animal and spontaneously epileptic rat (SER: zi/zi, tm/tm) that shows both tonic convulsion and absence-like seizures. LEV also has unique characteristics in terms of its antiepileptic mechanism; it has no activity on Na⁺ and K⁺ channels or on glutamate and GABA(A) receptors.

Na+/Ca2+ exchanger inhibitors inhibit neurite outgrowth in PC12 cells.

To elucidate the role of Na(+)/Ca(2+) exchanger (NCX) in neurite outgrowth, we investigated the effects of NCX inhibitors on neurite outgrowth in PC12 cells. KB-R7943 and 3',4'-dichlorobenzamil, NCX inhibitors, inhibited the neurite outgrowth caused by nerve growth factor (NGF). NCX inhibitors inhibited the neurite outgrowth caused by dibutylyl cAMP, which rapidly reorganizes the cytoskeleton.

Antidepressant-like effect of venlafaxine is abolished in μ-opioid receptor-knockout mice.

Although the opioid system is known to modulate depression-like behaviors, its role in the effects of antidepressants is not yet clear. We investigated the role of μ-opioid receptors (MOPs) in the effects of venlafaxine, a serotonin and norepinephrine reuptake inhibitor, in the forced swim test using MOP-knockout (KO) mice. Venlafaxine reduced immobility time in wild-type mice (C57BL/6J), but not in MOP-KO mice, although no significant effects were observed on locomotor activity.

Reduced emotional and corticosterone responses to stress in mu-opioid receptor knockout mice.

The detailed mechanisms of emotional modulation in the nervous system by opioids remain to be elucidated, although the opioid system is well known to play important roles in the mechanisms of analgesia and drug dependence. In the present study, we conducted behavioral tests of anxiety and depression and measured corticosterone concentrations in both male and female mu-opioid receptor knockout (MOP-KO) mice to reveal the involvement of mu-opioid receptors in stress-induced emotional responses. MOP-KO mice entered more and spent more time in the open arms of the elevated plus maze compared with wild-type mice.

Abolished thermal and mechanical antinociception but retained visceral chemical antinociception induced by butorphanol in mu-opioid receptor knockout mice.

Butorphanol is hypothesized to induce analgesia via opioid pathways, although the precise mechanisms for its effects remain unknown. In this study, we investigated the role of the mu-opioid receptor (MOP) in thermal, mechanical, and visceral chemical antinociception induced by butorphanol using MOP knockout (KO) mice. Butorphanol-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice.

Voltage-dependent calcium channel abnormalities in hippocampal CA3 neurons of spontaneously epileptic rats.

Purpose: Hippocampal CA3 neurons of spontaneously epileptic rats (SER; zi/zi, tm/tm), which show both absence-like seizures and tonic convulsions, exhibit a long-lasting depolarization shift with repetitive firing with a single stimulation of mossy fibers. Therefore a whole-cell patch-clamp study using temporarily dissociated hippocampal CA3 neurons from SER was performed to elucidate whether such abnormal excitability was due to abnormalities in voltage-dependent Ca(2+) channels (VDCCs).

Methods: Hippocampal CA3 neurons were temporarily dissociated with enzymatic and mechanical treatments.

Mu opioid receptor-dependent and independent components in effects of tramadol.

Tramadol is thought to induce analgesia via both opioid and non-opioid pathways, although the precise mechanisms remain to be elucidated. In this study, we investigated the roles of the mu-opioid receptor (MOP) in analgesic and rewarding effects of tramadol by using MOP knockout (KO) mice. Tramadol-induced antinociception, assessed by hot-plate and tail-flick tests, was significantly reduced in heterozygous and homozygous MOP-KO mice when compared with that in wild-type mice.

Long-lasting antiepileptic effects of levetiracetam against epileptic seizures in the spontaneously epileptic rat (SER): differentiation of levetiracetam from conventional antiepileptic drugs.

Purpose: Some evidence suggests that levetiracetam (LEV) possesses antiepileptogenic characteristics. The purpose of this study was to investigate the time course of seizure protection by LEV compared with that of phenytoin (PHT), phenobarbital (PB), valproate (VPA), and carbamazepine (CBZ) in the spontaneously epileptic rat (SER). The SER is a double mutant (tm/tm, zi/zi) showing both tonic convulsions and absence-like seizures.

Separation of antiepileptogenic and antiseizure effects of levetiracetam in the spontaneously epileptic rat (SER).

Purpose: The long-lasting antiseizure effects of levetiracetam (LEV) have been observed in the spontaneously epileptic rat (SER) that expresses both tonic and absence-like seizures. Furthermore, the antiepileptogenic effects of LEV in addition to antiseizure effects have been reported in the amygdala-kindling model in rats. This suggests that the long-lasting seizure protection of LEV may be at least partly due to its antiepileptogenic effects.

Augmentation of serotonin-induced inhibition of neuronal activity in the hippocampus following repeated treatment with methamphetamine.

Electrophysiological studies were performed to determine whether or not hippocampal serotonergic modulation was affected following repeated administration of methamphetamine (MAP). Rats were i.p.

Failure of repeated electroconvulsive shock treatment on 5-HT4-receptor-mediated depolarization due to protein kinase A system in young rat hippocampal CA1 neurons.

We previously demonstrated that repeated electroconvulsive shock (ECS) treatment enhanced serotonin (5-HT)(1A)- and 5-HT(3)-receptor-mediated responses in hippocampal CA1 pyramidal neurons. The electrophysiological studies were performed to elucidate the effects of ECS treatment on depolarization, which was an additional response induced by 5-HT, and the second messenger system involved in this depolarization of hippocampal CA1 neurons. Both application of 5-HT (100 microM) induced depolarization of the membrane potential in the presence of 5-HT(1A)-receptor antagonists.

Activation by N-acetyl-L-aspartate of acutely dissociated hippocampal neurons in rats via metabotropic glutamate receptors.

Purpose: We previously reported that an increase in the N-acetyl-L-aspartate (NAA) level due to the lack of aspartoacylase gene was found in the brain of the tremor rat (tm/tm), which is a mutant with a causative gene named tm that shows epileptic seizures. Therefore, NAA is suggested to be one of the factors involved in the induction of epileptic seizures. Patch-clamp studies were performed to determine whether NAA produces an excitatory effect on acutely dissociated rat hippocampal neurons.

Epileptiform burst discharges in hippocampal CA3 neurons of young but not mature Noda epileptic rats (NER).

Noda epileptic rat (NER), originally found in a colony of Crj; Wistar rats, shows spontaneous tonic-clonic convulsion characterized by the appearance of high voltage polyspikes in cortical and hippocampal EEG once every 2-3 days after 2-4 months of age. Electrophysiological studies using hippocampal slice preparations of NER were performed to determine whether hippocampal neurons have abnormal excitability. When a single stimulus (1-25 V) was delivered to the mossy fibers of NER at 4-6 weeks old before they showed any seizures, a long-lasting depolarization shift (DS) accompanied by repetitive firings and after-hyperpolarization following the abnormal firing was observed in seven of 14 hippocampal CA3 neurons.

Existence of ionotropic glutamate receptor subtypes in cultured rat retinal ganglion cells obtained by the magnetic cell sorter method and inhibitory effects of 20-hydroxyecdysone, a neurosteroid, on the glutamate response.

Glutamate and neurosteroids are known to exist in retinal ganglion cells (RGC). Therefore, patch clamp studies using the whole-cell recording method were performed to determine whether or not ionotropic glutamate receptor subtypes, i.e.

[Modulation of neuronal activities in the central nervous system via sigma receptors].

Sigma receptors have recently been the target of drug development related to psychiatric disorders, including schizophrenia and depression, as well as cognitive enhancers. This paper focused on the sigma-receptor-mediated modulation of neuronal activity, especially the effects on aminergic neuron and hippocampal neuron activity. Dopaminergic neuron activities in the substantia nigra and ventral tegmental area (VTA) are variously modified by the systemic administration of sigma ligands.

Enhancement of serotonin(1A) receptor function following repeated electroconvulsive shock in young rat hippocampal neurons in vitro.

Effects of repeated electroconvulsive shock (ECS) treatment on 5-hydroxytryptamine (5-HT) response were investigated to elucidate the ECS-induced changes, which may be related to antidepressant effects, using electrophysiological methods with hippocampal slices in vitro. ECS was applied to Wistar rats once daily for 14 d from 3 wk of age (ECS group). Control animals did not receive ECS (control group).