Primed-bursts induced long-term potentiation in rat visual cortex: effects of dark-rearing

Theta burst stimulation (TBS) and primed bursts (PBs) stimulation are among the effective tetanic stimulations for induction of long-term potentiation (LTP) in the hippocampus. Recent studies have indicated that TBS is effective in LTP induction of layer III synapses of neocortex, only if applied to layer IV. However, the possibility of neocortical LTP induction using PBs has not been investigated yet. Sensory deprivation greatly influences the development of neocortex. According to the effect of sensory deprivation on synaptic plasticity of developing neocortex, we studied the induction of LTP by PBs in visual cortical slices of control and dark-reared rats. The results showed that application of PBs to layer IV could effectively induce LTP of layer II/III field potentials. These potentials are consisted of two components: pEPSP1, (population excitatory postsynaptic potential 1) and pEPSP2. In control slices PBs led to selective potentiation of pEPSP2. Visual deprivation increased the incidence of LTP of pEPSP1 and decreased the amount of LTP of pEPSP2. These findings showed that PBs could be used as an effective tetanic stimulation to study the synaptic plasticity in neocortex. The effects of visual deprivation on PBs-induced LTP are consistent with its role in the development of excitatory system in neocortex.     

Persistence and Efficacy of Four Iranian Diatomaceous Earths Against Three Stored Grains Beetles

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Persistence and efficacy of four Iranian diatomaceous earth formulations was assessed against Sitophilus...     

Micromeritics and release behaviours of cellulose acetate butyrate microspheres containing theophylline prepared by emulsion solvent evaporation and emulsion non-solvent addition method

The present research work compares the effect of microsphere preparation technique on micromeritics and release behaviors of theophylline microspheres. Microspheres were prepared by oil-in oil (O₁/O₂) emulsion solvent evaporation method (ESE) using different ratios of anhydrous theophylline to cellulose acetate butyrate (CAB). Cyclohexane was used as non-solvent to modify the ESE technique (MESE method) and the effect of non-solvent volume on properties of microspheres was investigated. The obtained microspheres were analyzed in terms of drug content, particle size and encapsulation efficiency. The morphology of microsphere was studied using scanning electron microscope. The solid state of microspheres, theophylline and CAB were investigated using X-ray, FT-IR and DSC. The drug content of microspheres prepared by MESE method was significantly lower (15.54% ± 0.46) than microspheres prepared by ESE method (41.08 ± 0.40%). The results showed that as the amount of cyclohexane was increased from 2 mL to 6 mL the drug content of microspheres was increased from 15.54% to 28.71%. Higher encapsulation efficiencies were obtained for microspheres prepared by ESE method (95.87%) in comparison with MESE method (64.71%). Mean particle size of microsphere prepared by ESE method was not remarkably affected by drug to polymer ratio, whereas in MSES method when the volume of cyclohexane was increased the mean particle size of microsphere was significantly decreased. The ratio of drug to polymer significantly changed the rate of drug release from microspheres and the highest drug release was obtained for the microsphere with high drug to polymer ratio. The amount of cyclohexane did not significantly change the drug release. Although, x-ray showed a small change in crystallinity of theophylline in microspheres, DSC results proved that theophylline in microspheres is in amorphous state. No major chemical interaction between the drug and polymer was reported during the encapsulation process.     

Visual deprivation increases capability of layer II/III for epileptiform activity in the rat visual cortical slices

Effects of visual deprivation on the induction of epileptiform activity were studied in layer II/III of 29-39-day-old rat primary visual cortex. Field potentials were evoked by stimulation of layer IV in slices from control (CON) and dark-reared (DR) rats. Picrotoxin (PTX)-induced epileptiform activity was characterized by spontaneous and evoked epileptic field potentials (EFPs). The results showed that DR slices demonstrate greater susceptibility for induction of spontaneous EFP. PTX-induced changes in the characteristics of evoked field potentials also showed higher tendency of DR animals to generate epileptiform activity. In both groups, field potentials consisted of pEPSP(1) (population excitatory postsynaptic potential 1, i.e., first negativity) and pEPSP(2) (second negativity), respectively. There was no significant difference between the characteristics of field potentials in CON and DR slices. PTX significantly increased amplitude and duration of pEPSP(2), but it had no significant effect on pEPSP(1). Effects of PTX on pEPSP(2) were significantly higher in DR slices. It is concluded that visual deprivation results in a heightened potential in layer II/III of the rat visual cortex to generate PTX-induced epileptiform activity.     

Differential effect of dark rearing on long-term potentiation induced by layer IV and white matter stimulation in rat visual cortex

In the earlier work, we showed that primed-burst stimulation (PBs) is an effective protocol to induce long-term potentiation (LTP) in layer II/III of adult rat visual cortex in vitro. In the present study, we investigated effects of dark rearing on potentiation of layer II/III responses to stimulation of layer IV or the underlying white matter in the visual cortex in vitro. Long-term potentiation was induced by PBs applied to white matter or layer IV of the cortex in light and dark reared rats. Regardless of the stimulation site, layer II/III field potentials consisted of two components. In general, the latency of responses in dark reared rats was shorter than that in light reared ones. Whereas PBs of layer IV produced LTP of two components in both the groups, that of white matter induced an appreciable potentiation of the second component in both groups and the first component only in dark reared rats. These results indicate that PBs of either white matter or layer IV can gain access to the modifiable synapses that are related to the second component of layer II/III responses in light and dark reared visual cortex, but accessibility of the modifiable synapses that are related to first component depends on the tetanization site. The dark rearing enhances accessibility of the modifiable synapses that are related to the first component following PBs of the white matter. It is suggested that the immaturity of inhibitory circuits and/or better function of excitatory ones in the visual cortex of dark reared rats may contribute to the enhanced accessibility of the first component.     

Combined sub-threshold dosages of phenobarbital and low-frequency stimulation effectively reduce seizures in amygdala-kindled rats

Low-frequency stimulation (LFS) is a potential therapy utilized in patients who do not achieve satisfactory control of seizures with pharmacological treatments. Here, we investigated the interaction between anticonvulsant effects of LFS and phenobarbital (a commonly used medicine) on amygdala-kindled seizures in rats. Animals were kindled by electrical stimulation of basolateral amygdala in a rapid manner (12 stimulations/day). Fully kindled animals randomly received one of the three treatment choices: phenobarbital (1, 2, 3, 4 and 8 mg/kg; i.p.; 30 min before kindling stimulation), LFS (one or 4 packages contained 100 or 200 monophasic square wave pulses, 0.1-ms pulse duration at 1 Hz, immediately before kindling stimulation) or a combination of both (phenobarbital at 3 mg/kg and LFS). Phenobarbital alone at the doses of 1, 2 and 3 mg/kg had no significant effect on the main seizure parameters. LFS application always produced anticonvulsant effects unless applied with the pattern of one package of 100 pulses, which is considered as non-effective. All the seizure parameters were significantly reduced when phenobarbital (3 mg/kg) was administered prior to the application of the non-effective pattern of LFS. Phenobarbital (3 mg/kg) also increased the anticonvulsant actions of the effective LFS pattern. Our results provide an evidence of a positive cumulative anticonvulsant effect of LFS and phenobarbital, suggesting a potential combination therapy at sub-threshold dosages of phenobarbital and LFS to achieve a satisfactory clinical effect.     

Augmentation of LTP induced by Primed–Bursts tetanic stimulation in hippocampal CA1 area of morphine dependent rats

The effects of chronic morphine administration on the development of Long-term potentiation (LTP) were investigated at the Schaffer collateral-CA1 pyramidal cell synapses of the rat hippocampal slices using primed-bursts tetanic stimulation. Significant enhancement of orthodromic population spike (OPS) was found for all stimulus intensities after tetanic stimulation. OPS enhancement was greatest when tested with low to mid-range stimulus intensities (25 and 50 μA). There was also significant decrease in OPS delay. These responses were similar in slices from both control and morphine dependent rats. At all delivered stimulus intensities, the amount of LTP of OPS in slices from dependent rats was larger than that of control slices. However, these differences in LTP of OPS were significant at low stimulus intensities. These findings suggest that chronic morphine administration had induced changes in CA1 neurocircuitry which modulated synaptic plasticity during high frequency stimulation and appeared as augmented LTP.     

Differential modulatory actions of GABAA agonists on susceptibility to GABAA antagonists-induced seizures in morphine dependent rats: possible mechanisms in seizure propensity

In order to clarify the mechanisms involved in the susceptibility to GABA_A antagonists-induced seizures in morphine dependent rats, we investigated how GABA_A agonists modulate this vulnerability. Seizures were induced to animals by infusion of GABA_A antagonists: pentylenetetrazole (PTZ), picrotoxin (PIC) and bicuculline (BIC). GABA_A agonists, muscimol (MUS) and 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol (THIP), were administered intravenous (i.v.) before antagonists. Morphine-dependence significantly decreased the PTZ threshold dose (19.16 ± 1.89 versus 25.74 ± 1.25 mg/kg) while, it had no effect on PIC induced seizures. BIC doses for both threshold and tonic-clonic seizures induction were significantly lower in morphine dependent rats (0.10 ± 0.01 and 0.12 ± 0.02 versus 0.25 ± 0.02 and 0.39 ± 0.07 mg/kg respectively). In morphine-dependence, although pre-treatment with MUS significantly increased the required dose of PTZ for seizures threshold, THIP significantly decreased the required dose of PTZ for tonic-clonic convulsion. Moreover, MUS pretreatment completely recovered the effect of morphine dependency on BIC seizure activity.The results suggest that the capability of GABA_A agonists on modulation of propensity to seizures induced by different antagonists in morphine-dependence is dissimilar. Therefore, it seems that long-term morphine alters some properties of GABA system so that the responsive rate of GABA_A receptors not only to its antagonists, but also to its agonists will change differently.     

Enriched environment prevents cognitive and motor deficits associated with postnatal MK-801 treatment

Rationale

Previous studies have shown the beneficial effects of enriched environment (EE) in rescuing behavioral deficits such as pre-pulse inhibition and locomotor hyperactivity associated with N-methyl-D-aspartate (NMDA) receptor blockade; however, cognitive deficits remain unresponsive.

Objectives

We designed experiments to determine the consequences of raising rat pups in an EE on several behavioral aberrations, mainly cognitive deficits, observed in rats postnatally exposed to MK-801 (NMDA receptor antagonist).

Methods

Male Wistar rats were injected with MK-801 (1 mg/kg) from postnatal day (P) 6–10. Rat pups were housed in an EE from birth up to the time of behavioral experiments at P28–34. The effects of EE in correcting MK-801-associated behaviors were assessed by rotarod, wire grip, open filed, and Morris water maze tests.

Results

We found that EE not only has beneficial effects on cognitive performance of normal rats but also prevents spatial learning and memory deficits in Morris water maze induced by MK-801. Postnatal MK-801 treatment also led to motor deficits both in wire grip and accelerating rotarod tests. These deficits were not observed in MK-801-treated rats raised in EE. In the open field test, EE prevented increase in “frequency of grooming” and decrease in “time spent in the center” associated with MK-801.

Conclusions

Our results suggest that exposure to an EE would be strongly beneficial in correcting deficits, notably cognitive, associated with MK-801. Given that the postnatal MK-801 treatment represents an animal model of schizophrenia, we propose timely environmental interventions might be an effective strategy in the protection against schizophrenia.     

Chemical kindling and seizure susceptibility in morphine dependent rats

In the present study, we investigated whether and how chronic morphine administration changes seizure susceptibility in rats. The role of morphine-dependence on the seizure susceptibility has been evaluated with models of pentylenetetrazol (PTZ)-kindling and acute convulsions induced by PTZ, N-methyl-d-aspartic acid (NMDA), picrotoxin and caffeine in adult male rats. The results showed that morphine-dependence increased seizure severity only at 1–4th PTZ injections in the kindling model. In acute convulsion tests, dependent rats demonstrated a significantly lower seizure threshold only for PTZ, while they demonstrated a significantly lower tendency to show tonic–clonic convulsions only for NMDA. It is concluded that morphine-dependence may modulate PTZ-kindling and seizure susceptibility in rats with emphasis on the role of GABA and NMDA neurotransmitter systems.