The effect of peripheral administration of growth hormone on AD-like cognitive deficiency in NBM-lesioned rats.

This study aimed to evaluate the peripheral administration of growth hormone (GH) on AD-like cognitive deficiency in NBM-lesioned rats induced by ibotenic acid (5 microg/microl, in each side). Forty-eight male Wistar rats (20-24 months old; weighing 330+/-30 g) randomly divided into six groups (n=8). The groups include control group, which were intact rats; n-L+GH group: non-lesioned rats with GH treatment (1mg/kg, 9.00 am, for 10 consecutive days); n-L+Veh group: non-lesioned rats with vehicle treatment; L group: NBM-lesioned rats; L+GH group: NBM-lesioned rats with GH treatment and L+Veh group: NBM-lesioned rats with same volume of vehicle treatment. Peripheral administration of GH in control had no effect on learning and memory, while in L+GH group produced a significant enhancement in spatial learning and memory comparing to L and L+Veh groups. The percent of time spent in goal quarter during probe trial has decreased significantly in L and L+Veh groups compared to n-L groups. While it has increased significantly in L+GH group compared to L and L+Veh groups. No significant difference in percent of time spent was seen between the control and n-L groups. The GH has known as a mediate that effect through IGF-1. As the IGF-1 itself is earlier shown to improve cognitive function it is likely that the observed effect of GH is mediated through release of IGF-1 from peripheral tissue into the circulation for further transport across the BBB. This mechanism may result in the improvement of learning and memory in rats with NBM lesion.

Effect of reversible inactivation of locus ceruleus on spatial reference and working memory.

The locus coeruleus (LC) is the largest source of norepinephrine (NE) in the prefrontal cortex and the hippocampus, influencing the cognitive functions of these areas. All previous studies have studied the role of the LC-NE system on learning and memory using the irreversible lesion technique, employing either electrocoagulation or excitotoxins. However, the reversible functional inactivation of LC by means of stereotaxic local microinjection of lidocaine could measure the phases of memory processing (acquisition, consolidation and retention) without any interference with the other cognitive functions of the same structure either during earlier or later phases of the same process. The aim of this study is to investigate LC involvement in spatial reference and working memory by inducing bilateral pre-training, post-training and pre-retrieval lidocaine functional inactivation using the Morris water maze task. The reversible inactivation of LC was applied at different stages of spatial memory formation: (1) immediately before the training sessions to determine the effects on acquisition of the both reference and working memory; (2) immediately after the training session to evaluate effects on both spatial memory consolidation and retention of working memory; and (3) immediately before the 24 h retention session to analyze the effects on the retrieval process of reference memory. Our results indicate that the bilateral reversible inactivation of LC significantly impaired the acquisition of reference and working memory, while it had no effect on consolidation and/or retention of such memories in the Morris water maze (MWM) task. Therefore, the noradrenergic system of the LC may play a more important role in acquisition than in consolidation and retrieval of spatial memory in wistar rats.

The role of adenosine A(1) receptors in mediating the inhibitory effects of low frequency stimulation of perforant path on kindling acquisition in rats.

Low frequency stimulation (LFS) has an inhibitory effect on rapid perforant path kindling acquisition. In the present study the role of adenosine A(1) and A(2A) receptors in mediating this inhibitory effect was investigated. Rats were kindled by perforant path stimulation using rapid kindling procedures (12 stimulations per day). LFS (0.1 ms pulse duration at 1 Hz, 200 pulses, and 50-150 muA) was applied to the perforant path immediately after termination of each rapid kindling stimulation. 1,3-Dimethyl-8-cyclopenthylxanthine (CPT; 50 muM), a selective A(1) antagonist and ZM241385 (ZM, 200 muM), a selective A(2A) antagonist were daily microinjected into the lateral ventricle 5 min before kindling stimulations. LFS had an inhibitory effect on kindling development. Pretreatment of animals with CPT reduced the inhibitory effect of LFS on kindling rate and suppressed the effects of LFS on potentiation of population EPSP during kindling acquisition. In addition, CPT was able to antagonize the effects of LFS on kindling-induced increase in early (10-50 ms intervals) and late (300-1000 ms intervals) paired pulse depression. ZM pretreatment had no effect on antiepileptogenic effects of LFS in kindling acquisition. In addition, LFS prevented the kindling-induced elevation of cyclic AMP (cAMP) levels in kindled animals. Based on these results, we suggest that the antiepileptogenic effects of LFS on perforant path kindling might be mediated through activation of adenosine A(1), but not A(2A) receptors. Moreover, modulation of cAMP levels by LFS may potentially be an important mechanism which explains the anticonvulsant effects of LFS in kindled seizures.

Lidocaine reversible inactivation of the median raphe nucleus has no effect on reference memory but enhances working memory versions of the Morris water maze task.

Numerous studies in the past have dealt with the role of serotonergic system lesions in tasks aimed at measurement of cognitive behavior, but the literature concerning the role of serotonin in cognition remains controversial. Rats with electrolytic lesions of the median raphe nucleus (MRN) were found to display a profound impairment in both the acquisition and retention of spatial memory task. In this study, the lidocaine inactivation was employed to evaluate the involvement of the rat's median raphe nucleus in reference and working memory versions of the Morris water maze (MWM) task. Lidocaine (0.5 microl, 2%) was injected through a single cannula aimed at the MRN; control groups were treated in the same way with a 0.5 microl injection of saline. In Experiment 1, rats were trained in a reference memory version of the MWM with two blocks of four trials per day for three consecutive days, with intra-cerebral injection made 5 min before training. No significant difference was found. In Experiment 2, intra-cerebral injection was applied immediately after two blocks of four trials, and in Experiment 3, the drug was injected 5 min before retention test in rats that had received eight trials per day on three consecutive days. Again, no significant difference between control and treatment groups was found. These results indicate that MRN has no role in acquisition, consolidation and retrieval of spatial reference memory. In subsequent experiments, rats were trained in a working memory version of the MWM task to find a new target position in trial 1, and retrieval was tested 75 min later. MRN inactivation 5 min before (Experiment 4) and immediately after the acquisition trial (Experiment 5) enhanced spatial working memory. It is concluded that normal activity of the MRN has no role in formation and retrieval of reference memory, but it has an inhibitory role in working memory. Our results are confirmed with other studies suggesting that the serotonergic system has a different role in long-term and short-term memory. Interaction with other neurotransmitter systems like acetylcholine may be involved in this case.

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.

Adenosine A(2) receptors inhibit morphine self-administration in rats.

In the present study, the effect of adenosine receptor agonists and antagonists on morphine self-administration was investigated. Intravenous administration of morphine (0.3-3 mg/kg/injection) induced dose-dependent self-administration. The adenosine receptor antagonists, theophylline (2.5, 5, 10 mg/kg) and 3, 7-Dimethyl-1-propargylxanthine (DMPX; 0.25, 0.5, 1 mg/kg), when injected 1 h before the start of the test, reduced the number of self-administered morphine infusions. The adenosine receptor antagonists when administered in the training period (11 days) greatly increased the number of morphine infusions, however, they did not induce any response by themselves. 5'-N-ethylcarboxamido-adenosine (NECA; 0.5, 1 mg/kg) and 4-[2-[[6-Amino-9-(N-ethyl-beta-D-ribofuranuronamidosyl)-9H-purin-2 -yl ]amino] ethyl]benzenepropanoic acid (CGS21680; 0.001, 0.01, 0.025, 0. 05 mg/kg), given 1 h before the start of the test, increased morphine self-administration. Although the adenosine agonists, when injected during training period (11 days), reduced morphine self-administration. Furthermore, NECA, but not CGS21680, induced significant self-administration. The adenosine A(1) receptor agonist, N(6)-cyclohexyladenosine (CHA; 0.01, 0.1, 0.25, 0.5 and 1 mg/kg), and the adenosine A(1) receptor antagonist, 8-phenyletheophylline (2, 4, 6, 8 mg/kg), themselves neither altered morphine infusion nor induced any response. These results indicate a role for adenosine A(2) receptors in the expression and/or development of morphine self-administration.

Primed-burst potentiation in adult rat visual cortex in vitro.

The effectiveness of θ pattern primed-bursts (PBs) on development of PB potentiation was investigated in layer II/III of the adult rat visual cortex in vitro. Experiments were carried out in the visual cortical slices. Population excitatory postsynaptic potentials (pEPSPs) were evoked in layer II/III by stimulation of either white matter or layer IV. To induce long-term potentiation (LTP), eight episodes of PBs were delivered at 0.1 Hz. Regardless of stimulation site, field potential recorded in layer II/III consisted of two components: a short latency and high amplitude response called pEPSP1, and a long latency and low amplitude response called pEPSP2. The incidence of LTP produced by PBs of layer IV was higher than that of the white matter tetanization. In contrast, PBs of both layer IV and white matter reliably produced LTP of pEPSP2 in layer II/III. It is concluded that PBs, as a type of activity pattern, of either white matter or layer IV can gain access to the modifiable synapses that are related to pEPSP2 in layer II/III, but accessibility of the modifiable synapses that are related to pEPSP1 depends on tetanization site. Relevancy of the results to the plasticity gate hypothesis is also discussed.

Chronic in vivo morphine administration facilitates primed-bursts-induced long-term potentiation of Schaffer collateral-CA1 synapses in hippocampal slices in vitro.

In this study, the effects of chronic morphine administration (20-30 days) on long-term potentiation (LTP) were investigated at the Schaffer collateral-CA1 pyramidal cell synapses of the rat hippocampal slices. Orthodromic population spike (OPS) amplitude and delay (peak latency) were measured as indices of increase in synaptic efficacy. The amounts of LTP of OPS delay and LTP of OPS amplitude were higher in slices from dependent rats. Perfusion of slices from control and dependent rats with morphine containing ACSF and delivering tetanic stimulation, showed that short-term presence of morphine could not mimic the LTP enhancing effects of chronic morphine administration, however, attenuated the amount of LTP of OPS amplitude in slices of dependent rats. This study supports the hypothesis that the susceptibility of CA1 synapses to plastic changes increases by chronic, not acute exposure to morphine and suggests that a withdrawal phenomenon might be an underlying mechanism for the observed augmented LTP of OPS amplitude in slices of dependent rats.

Reversible inactivation of the median raphe nucleus enhances consolidation and retrieval but not acquisition of passive avoidance learning in rats.

Involvement of median raphe nucleus (MRN) in acquisition, consolidation and retrieval of passive avoidance (PA) was investigated with functional suppression of this area by lidocaine. Rats carrying a chronically implanted cannula aimed at the MRN were trained on a step-through passive avoidance task and received intra-MRN injection of lidocaine or saline 5 min before training or 5, 90 and 360 min after acquisition trial or 5 min before the retrieval test. Lidocaine MRN inactivation had no effect on PA learning. Lidocaine injected 5 and 90 min after the acquisition trial significantly enhanced avoidance of the dark compartment in comparison with the control group injected with saline. But PA retention was not affected by lidocaine injected 360 min after acquisition or 5 min before training. Retention latency significantly increased, when lidocaine injected 5 min before retrieval test. Step-through latency of naive rats was not affected by MRN blockade. Furthermore, reversible inactivation of MRN did not have a significant effect on locomotor activity. Our results indicate that the MRN contributes to PA consolidation at least until 90 min after acquisition and involves in PA retrieval. It is concluded that functional ablation of the MRN may disrupt the inhibitory actions of MRN projections to sub-cortical circuits participating in PA memorization and retrieval.

Involvement of NMDA receptors and voltage-dependent calcium channels on augmentation of long-term potentiation in hippocampal CA1 area of morphine dependent rats.

The involvement of NMDA receptors and voltage-dependent calcium channels on augmentation of long-term potentiation (LTP) was investigated at the Schaffer collateral-CA1 pyramidal cell synapses in hippocampal slices of morphine dependent rats, using primed-bursts tetanic stimulation. The amplitude of population spike was measured as an index of increase in postsynaptic excitability. d, l-AP5 and nifedipine were used as NMDA receptor antagonist and voltage-dependent calcium channel blocker, respectively. The amount of LTP of orthodromic population spike amplitude was higher in slices from dependent rats. Perfusion of slices from control or dependent rats with ACSF containing either D,L-AP5 (25 microM) or nifedipine (10 microM) and delivering tetanic stimulation, showed that D,L-AP5 completely blocked LTP of OPS in slices from both control and dependent rats, while nifedipine attenuated the amount of LTP of OPS in dependent slices and had no effect on control ones. The results suggest that the enhanced LTP of OPS in the CA1 area of hippocampal slices from morphine dependent rats is primarily induced by the NMDA receptors activity and the voltage-dependent calcium channels may also be partially involved in the phenomenon.

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.

Examination of persistent effects of repeated administration of pentylenetetrazol on rat hippocampal CA1: evidence from in vitro study on hippocampal slices.

The early and long-lasting effects of pentylenetetrazol-kindling on hippocampal CA1 synaptic transmission were investigated. Experiments were carried out in the hippocampal slices from control and kindled rats at two post-kindling periods, i.e. 48-144 h (early phase) and 30-33 days (long-lasting phase). Field potentials, i.e. population excitatory postsynaptic potential (pEPSP) and population spike (PS) were recorded at the stratum pyramidale following stimulation of the stratum radiatum. Kindling-induced changes in synaptic transmission were assessed by stimulus-response functions and paired-pulse responses. The results showed that 48-144 h after kindling, the PS amplitude in the CA1 of kindled slices enhanced, and a second PS appeared compared to control slices. But at 30-33 days after kindling, the pEPSP slope in the CA1 of kindled slices enhanced without any change in the PS compared with those in the control slices. Evaluation of paired-pulse responses showed a significant reduction in paired-pulse inhibition for PS 48-144 h after kindling and a significant increase in paired-pulse inhibition for pEPSP 30-33 days after kindling. Our results suggest that pentylenetetrazol-kindling is accompanied by enhanced excitability and a reduction of paired-pulse inhibition in hippocampal CA1. The increased paired-pulse inhibition one month after kindling, may be interpreted as an adaptive process to cope with subsequent seizures.

Repeated administration of pentylenetetrazol alters susceptibility of rat hippocampus to primed-burst stimulation: evidence from in vitro study on CA1 of hippocampal slices.

The effectiveness of theta pattern primed-bursts (PBs) on development of primed-burst (PB) potentiation was investigated in hippocampal CA1 of pentylenetetrazol-kindled rats. Experiments were carried out in the hippocampal slices from control and kindled rats at two post-kindling periods, i.e., 48-144 h (early phase) and 30-33 days (long-lasting phase). Field potentials (population excitatory post-synaptic potential, pEPSP) were recorded at stratum radiatum following stimulation of the stratum fibers. theta pattern primed-bursts were delivered to stratum radiatum and PB potentiation was assessed. The results showed that 48-144 h after kindling, PB potentiation in CA1 of kindled slices is significantly greater than control slices. In contrast, 30, 33 days after kindling PB potentiation was not observed and the pEPSP slope was depressed after PBs delivery, which lasted at least 60 min. Our results suggest that shortly after kindling, PB potentiation can be more readily induced while one month later, it is more difficult ot elicit. These findings may help to explain the behavioral deficits seen with the kindling model of epilepsy.

Effects of reversible inactivation of the medial septal area on long-term potentiation and recurrent inhibition of hippocampal population spikes in rats.

We assessed the effects of reversible inactivation of the medial septal area (MSA) on long-term potentiation (LTP) and recurrent inhibition in the dentate gyrus of urethane-anesthetized rats, in vivo. The septal input to the hippocampus was temporarily eliminated by injection of tetrodotoxin (TTX, 10 ng/l microliter) into the MSA. In Experiment 1, LTP inducibility was examined in the perforant-dentate gyrus synapses in the MSA inactivated and control rats by 2 high-frequency stimulation (HFS), 5 min apart, applied to the perforant pathway (PP). The magnitude of potentiation was evaluated as the percentage change in the population spike (PS) amplitude at 5, 30, 60 or 120 min after the second HFS. The PS amplitude in the MSA inactivated rats was significantly lower than those of control group at 120 but not 5, 30 or 60 min after the second HFS. The MSA inactivation itself had no effect on the basal responses evoked by test stimuli. In Experiment 2, the MSA inactivation did not affect the efficacy of recurrent inhibition in the perforant-dentate gyrus synapses produced by paired pulses applied to the PP at 10- and 20-ms interpulse intervals. These results indicate that: (1) although hippocampal synapses can be still potentiated after the HFS in the MSA inactivated animals, a faster decay of LTP may be due to elimination of the MSA output amplification on synaptic responses mediated by excitatory amino acids; and (2) the recurrent inhibition mechanism in the dentate gyrus of the hippocampus is not probably affected by the MSA inactivation.

Effects of reversible inactivations of the medial septal area on reference and working memory versions of the Morris water maze.

Involvement of the medial septal area (MSA) in reference memory and working memory versions of the Morris water maze (MWM) task was investigated in rats with reversible inactivation of this area by drugs injected through a single cannula aimed at the MSA. In Experiment 1, rats were trained in a reference memory version of the MWM with two blocks of four trials per day for 3 consecutive days. Acquisition was impaired by pretrial MSA injection of 10 ng tetrodotoxin (TTX) in 1 microliter saline but not of saline alone into MSA. In Experiment 2, intraseptal injection of TTX (10 ng, 1 microliter) immediately after two blocks of four trials had no effect on the consolidation of spatial reference memory. In Experiment 3, intraseptal injection of TTX (10 ng, 1 microliter) impaired retrieval of well established spatial reference memory in rats which had received 8 trials per day for 3 consecutive days. In Experiments 4 and 5, rats were trained in a working memory version of MWM task to find a new target position in trial 1 and retrieval of this information was tested 75 min later in trial 2. Intraseptal injection of lidocaine (4%, 1 microliter) prior to training impaired working memory performance while immediately posttraining injection of lidocaine had no effect. It is concluded that normal activity of the MSA is necessary for the memory formation at the time of training but its involvement in posttraining consolidation is unlikely. The MSA function is required for retrieval of well established spatial reference memory.

Bombesin-induced anorexia requires central bombesin receptor activation: independence from interaction with central catecholaminergic systems.

Intraperitoneal (IP) administration of bombesin (BBS; 2.5-20 micrograms/kg) induced a dose-dependent inhibition of food intake. The effect was decreased by intraventricular (ICV) administration of bombesin receptor antagonist [Leu14-psi (CH2NH)-Leu13] (3 micrograms/rat) but not by the D1 antagonist SCH 23390, the D2 antagonists sulpiride and pimozide, the dopamine antagonist cis-flupentixol, adrenoceptor blockers phenoxybenzamine or propranolol and serotonergic antagonist methergoline. It is concluded that BBS-induced suppression of feeding may be mediated through central BBS receptors, and is independent of interaction with brain catecholaminergic system.

Effect of D-1 or D-2 receptor stimulation on memory retrieval in mice.

Mice were trained in one-way active avoidance procedure and retention was tested at 4, 8, 16 and 24 h after training of animals and compared with non-shocked or untrained animals. The effect of drugs was tested on retrieval 24 h after training in other groups of mice. High doses of apomorphine or bromocriptine impaired, while low doses of the drugs improved, retrieval of avoidance. High doses of sulpiride reversed the impairment induced by high doses of these dopamine agonists. Low doses of sulpiride antagonized the improvement of retrieval induced by low doses of apomorphine. SKF 38393 treatment of animals also improved the retrieval. The retrieval impairment induced by higher doses of apomorphine or the improvement induced by different doses of SKF 38393 was antagonized by SCH 23390 pre-treatment. Single administration of SCH 23390 or low doses of sulpiride also impaired retrieval. It is concluded that stimulating post-synaptic D-2 dopamine receptors impairs retrieval whilst activation of pre-synaptic D-2 or post-synaptic D-1 receptors improves memory retrieval.

Evidence that low-threshold muscle afferents evoke long-latency stretch reflexes in human hand muscles.

1. The aim of the present study was to identify the type of spinal afferents involved in the generation of the long-latency response in intrinsic human hand muscles. Position-controlled extensions were imposed on the index finger or on the wrist of healthy subjects who were exerting a steady voluntary flexion force at the relevant joint. Averaged surface electromyographic (EMG) responses of the first dorsal interosseus muscle (FDI) or of the wrist flexors were evaluated with respect to latency and size. 2. Small transient angular displacements of the index finger (1 degree, as measured at the metacarpophalangeal joint), which are supposed to excite primary rather than secondary afferents, evoked two clearly discernible EMG responses with mean latencies of 32.3 ms (M1 response) and 54.7 ms (M2 response), respectively. The size of the M2 response exceeded the size of the M1 response by 60%. In the wrist flexors, transient stretch (1 degree) gave rise to a large M1 response (latency 22.8 ms) and a small, inconstent M2 response. 3. Small-amplitude vibration of the index finger elicited EMG responses in the FDI that were qualitatively and quantitatively similar to those seen in response to small transient stretches of the index finger. This was also true for fast ramp-and-hold stretches (stretch velocity 400 degrees/s, amplitude 5 degrees), whereas slow ramp-and-hold stretches (125 degrees/s, 5 degrees) elicited predominantly M2 responses. 4. In the FDI, the mechanical threshold of the M1 and M2 response to the transient angular displacement was approximately 0.15 degrees, with a tendency for the M2 response to appear at a lower threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Page kidney resulting from massive subcapsular hematoma. Complication of lumbar sympathetic nerve block.

The Page kidney is a recognized cause of hypertension. A massive subcapsular hematoma caused by a lumbar sympathetic nerve block resulted in a Page kidney. To our knowledge, this sequence has not been reported. Small hematomas may be treated conservatively, but massive subcapsular hematomas should be decompressed when the patient is clinically stable. Diagnostic features, therapeutic considerations, and pertinent references are discussed.