Sex-specific restoration of MK-801-induced sensorimotor gating deficit by environmental enrichment.

Despite ample evidence of N-methyl-D-aspartate (NMDA) receptor dysfunction in schizophrenia, no study has addressed the effects of enriched environment (EE) on sensorimotor gating deficits induced by postnatal NMDA receptor blockade. We evaluated the effect of EE on sensorimotor gating (measured by prepulse inhibition, PPI), or on sensorimotor gating deficit induced by the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) in both sexes of Wistar rats. Rats were injected with MK-801 (1 mg/kg) on postnatal days (P) 6-10. EE was provided from birth up to the time of experiments on P28-30 or P58-60. PPI data were collected at three prepulse intensities and then averaged to yield global PPI. MK-801 treatment reduced PPI significantly in both sexes. While EE per se had no significant effect on PPI, it restored MK-801-induced PPI deficit only in male rats. An extended period of EE did not influence PPI deficit in female rats. Our results indicate that postnatal exposure to MK-801 may exert long-lasting effects on neuronal circuits underlying sensorimotor gating. Sex-specific modulation of such effects by EE suggests sexually dimorphic mechanisms are involved.

Safety margin in excision of basal cell carcinoma.

The aim of this study was to evaluate the intact margin after surgery regarding common method with consideration of 4 mm safe margin. Fifty patients with basal cell carcinoma operated in Tabriz Sina hospital, were chosen randomly and pathological report of these patients after surgery was evaluated with consideration of presence of intact margin. In pathologic report before operation of these patients, Basal cell carcinoma was certified. Also, brief data of these patients history was studied from present cases. Forty eight of 50 (96%) patients had intact margin after surgery and just in two patients (4%), lesion was excised insufficiently and they had involved margin. With brief study of patients' history, most of them had advanced ages and the most common site of tumor presentation was head and neck. The most of these patients had exposure with so much sun light that was accounted an important etiology. With comparison of mentioned statistical results with other reports from other countries, this rate is considered in acceptable range and surgical method is done properly in this hospital and consideration of 4 mm of tumoral margin is enough.

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.

Effects of ketamine on synaptic transmission and long-term potentiation in layer II/III of rat visual cortex in vitro.

The effects of ketamine, which has NMDA receptor antagonist properties, on synaptic transmission and long-term potentiation in layer II/III of adult rat visual cortex were examined in vitro. Field potentials were recorded in layer II/III following layer IV stimulation. Primed-burst stimulation was used for induction of long-term potentiation. Stimulation of layer IV resulted in a two-component response in layer II/III, a population excitatory postsynaptic potential1 (EPSP1) and a population excitatory postsynaptic potential2 (EPSP2). DL-2-Amino-5-phosphono-valeric acid (AP5), a competitive NMDA receptor antagonist, reduced the amplitude of the population EPSP1 while ketamine increased the amplitude of the population EPSP2. The results showed that primed-burst stimulation induced long-term potentiation in layer II/III of the visual cortex in vitro. Preincubation for 30 min with AP5 (25-100 microM) reduced the extent of long-term potentiation of the population EPSP2 and blocked the induction of long-term potentiation of the population EPSP1. When ketamine (100-200 microM) was present for 30 min prior to tetanic stimulation, it blocked the induction of long-term potentiation of the population EPSP1 and reduced the extent of long-term potentiation of the population EPSP2. We conclude that ketamine can interfere with synaptic transmission in the visual cortex. Primed-burst stimulation is an effective protocol for neocortical potentiation. NMDA receptors are involved in the induction of long-term potentiation by primed-burst stimulation of the population EPSP1 and population EPSP2 in adult rat visual cortex in vitro.

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.

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.

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.

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 microA). 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.