Effects of lidocaine reversible inactivation of the median raphe nucleus on long-term potentiation and recurrent inhibition in the dentate gyrus of rat hippocampus

Hydrogen peroxide (H₂O₂) causes oxidative stress and is considered a mediator of cell death in various organisms. Our previous studies showed that prolonged (>6 h) treatment of Aplysia sensory neurons with 1 mM H₂O₂ produced hyperpolarization of the resting membrane potential, followed by apoptotic morphological changes. In this study, we examined the effect of H₂O₂ on the membrane conductance of Aplysia sensory neurons. Hyperpolarization was induced by 10 mM H₂O₂ within 1 h, and this was attributed to increased membrane conductance. In addition, treatment with 10 mM H₂O₂ for 3 min produced immediate depolarization, which was due to decreased membrane conductance. The H₂O₂-induced hyperpolarization and depolarization were completely blocked by dithiothreitol, a disulfide-reducing agent. The later increase of membrane conductance induced by H₂O₂ was completely blocked by 100 mM TEA, a K⁺ channel blocker, suggesting that H₂O₂-induced hyperpolarization is due to the activation of K⁺ conductance. However, the inhibition of K⁺ efflux by TEA did not protect against H₂O₂-induced cell death in cultured Aplysia sensory neurons, which indicates that the signal pathway leading to H₂O₂-induced cell death is more complicated than expected.     

The role of adenosine A1 and A2A receptors of entorhinal cortex on piriform cortex kindled seizures in rats.

In this research the role of adenosine A1 and A2A receptors of the entorhinal cortex on piriform cortex kindled seizures was investigated. In piriform cortex kindled rats, N6-cyclohexyladenosine (CHA), a selective A1 receptor agonist, 1,3-dimethyl-8 cyclopenthylxanthine (CPT), a selective A1 receptor antagonist, CGS21680 hydrochloride (CGS), a selective A2A receptor agonist and ZM241385 (ZM), a selective A2A receptor antagonist were injected into the entorhinal cortex bilaterally. Five minutes later, animals were stimulated and seizure parameters were recorded. CHA (10 and 100microM) decreased the afterdischarge duration (ADD), stage 5 seizure duration (S5D), and seizure duration (SD), and increased the latency to stage 4 of the seizure (S4L) significantly. Bilateral microinjection of CPT (100microM) increased ADD, S(5)D, and SD, and reduced S(4)L significantly. Pretreatment of animals with CPT (50microM) before CHA (100microM), reduced the effect of CHA on seizure parameters. On the other hand, CGS (1mM) increased only ADD. Bilateral microinjection of ZM had no effect on seizure parameters. However, pretreatment of animals with ZM (200microM) before CGS (1mM), eliminated the excitatory effect of CGS on seizure parameters. These results suggest that activation of A1 receptors of the entorhinal cortex has an anticonvulsant, but activation of A2A receptors of this region has a proconvulsive effect on piriform cortex kindled seizures.     

Antinociceptive effect of intra-hippocampal CA1 and dentate gyrus injection of MK801 and AP5 in the formalin test in adult male rats

Previous research has shown that the hippocampus processes pain related-information, probably through hippocampal neurons that respond exclusively to painful stimulation. In the current experiments we tested whether blocking NMDA receptors in the hippocampal CA1 region and dentate gyrus could reduce nociceptive behaviors in rats. The competitive and noncompetitive NMDA receptor antagonists 2-amino-5-phosphonopentanoic acid (AP5; 3.75 microg/0.75 microl) and MK801 (1.5, 3, 6 microg/0.5 microl) were injected into the dentate gyrus and CA1 area of behaving rats 5 min before subcutaneous injection of formalin irritant. Pain behaviors in both acute and tonic phases of the formalin test were significantly reduced by AP5 (3.75 microg/0.75 microl) and MK801 (3 microg/0.5 microl, but not 1.5 and 6 microg/0.5 microl) injection to the dentate gyrus. In the CA1, injection of AP5 had no effect while injection of the effective dose of MK801 (3 microg/0.5 microl) had a significant antinociceptive effect. This effect was apparent only during the late phase of the formalin test. These results support the hypothesis that NMDA-sensitive mechanisms are involved in acute and persistent pain-related processing in the dentate gyrus and with tonic pain processing in the hippocampal CA1 region.     

Fatalities following skin exposure to arsenic

Arsenic is a toxic metal that can cause death following exposure. In an unusual event, seven patients unintentionally applied a 30% arsenic solution to their entire body instead of a benzyl benzoate solution to treat their scabies. Hours later they developed severe skin reactions, including bullae, and were admitted to the hospital with gastrointestinal and cardiovascular disorders. Despite therapeutic interventions, three patients died and the rest were discharged from hospital with neurological sequelae. Toxicological analysis confirmed the presence of arsenic in the solution used by patients.     

Microinjection of ritanserin into the CA1 region of hippocampus improves scopolamine-induced amnesia in adult male rats

The effect of ritanserin (5-HT2 antagonist) on scopolamine (muscarinic cholinergic antagonist)-induced amnesia in Morris water maze (MWM) was investigated. Rats were divided into eight groups and bilaterally cannulated into CA1 region of the hippocampus. One week later, they received repeatedly vehicles (saline, DMSO, saline+DMSO), scopolamine (2 microg/0.5 microl saline/side; 30 min before training), ritanserin (2, 4 and 8 microg/0.5 microl DMSO/side; 20 min before training) and scopolamine (2 microg/0.5 microl; 30 min before ritanserin injection)+ritanserin (4 microg/0.5 microl DMSO) through cannulae each day. Animals were tested for four consecutive days (4 trial/day) in MWM during which the position of hidden platform was unchanged. In the fifth day, the platform was elevated above the water surface in another position to evaluate the function of motor, motivational and visual systems. The results showed a significant increase in escape latencies and traveled distances to find platform in scopolamine-treated group as compared to saline group. Ritanserin-treated rats (4 microg/0.5 microl/side) showed a significant decrease in the mentioned parameters as compared to DMSO-treated group. However, scopolamine and ritanserin co-administration resulted in a significant decrease in escape latencies and traveled distances as compared to the scopolamine-treated rats. Our findings show that microinjection of ritanserin into the CA1 region of the hippocampus improves the scopolamine-induced amnesia.     

Epileptogenic insult alters endogenous adenosine control on long‐term changes in synaptic strength by theta pattern stimulation in hippocampus area CA1

The impact of theta patterning of the stimulation on the kindling effects of pentylenetetrazol (PTZ) was studied in rat hippocampus area CA1 in vitro. A potential involvement of adenosine A1 receptors was also examined. Primed‐bursts stimulation (PBs) and theta pulse stimulation (TPS) were used as patterned activities. Stimulus patterns were applied to the Schaffer collateral afferents of hippocampal slices from both control and PTZ‐kindled rats, the field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) were simultaneously recorded from stratum radiatum and stratum pyramidale, respectively. Experiments were carried out in the presence or absence of the adenosine A1 receptor antagonist CPX. The following changes in kindled vs. control slices were observed. PBs was unable to produce both fEPSP LTP and PS LTP in untreated slices. When A1 receptor antagonist CPX was applied before PBs, both fEPSP LTP and PS LTP were elicited. PS LTP was selectively depressed by TPS (applied at 60 min after LTP induction) exclusively when A1 receptors were blocked, while TPS failed to depress PS LTP in untreated PBs‐exposed slices. These findings suggest that seizing entails lasting changes in hippocampus area CA1 so that LTP induction by PBs is masked due to intensive adenosine release which in turn prevents TPS to induce PS LTD in epileptic CA1 network. Synapse, 2010. © 2010 Wiley‐Liss, Inc.