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R Roesler

Publications and source records attributed to R Roesler.

At least 19 recordsLinked to original sources
PubMed2000

Guanosine impairs inhibitory avoidance performance in rats.

The nucleoside guanosine, previously found to exert trophic and neuroprotective effects, was found to impair retention of inhibitory avoidance responses, with a complete effect at 7.5 mg/kg i.p. pretraining. Treated animals, when retrained 1 week later, showed normal learning ability. Guanosine injected immediately after training or pretest did not alter retention latency. Combined pretraining and pretest treatments with guanosine failed to reverse its amnestic effect, excluding the contribution of state dependency. Open field parameters and shock sensitivity were mostly unaltered by guanosine. These results suggest an amnestic effect of guanosine on inhibitory avoidance in rats, in a pattern compatible with inhibition of glutamatergic activity. However, the mechanism for the amnestic effect of guanosine is yet to be elucidated.

Animals↗
PubMed2000

Cellular prion protein binds laminin and mediates neuritogenesis.

Laminin (LN) plays a major role in neuronal differentiation, migration and survival. Here, we show that the cellular prion protein (PrPc) is a saturable, specific, high-affinity receptor for LN. The PrPc-LN interaction is involved in the neuritogenesis induced by NGF plus LN in the PC-12 cell line and the binding site resides in a carboxy-terminal decapeptide from the gamma-1 LN chain. Neuritogenesis induced by LN or its gamma-1-derived peptide in primary cultures from rat or either wild type or PrP null mice hippocampal neurons, indicated that PrPc is the main cellular receptor for that particular LN domain. These results point out to the importance of the PrPc-LN interaction for the neuronal plasticity mechanism.

Animals↗
PubMed2000

Learning-specific decrease in synaptosomal ATP diphosphohydrolase activity from hippocampus and entorhinal cortex of adult rats.

Considering the involvement of extracellular ATP in the memory formation, we analyzed the effect of inhibitory avoidance training on ectonucleotidase activities in synaptosomes from hippocampus, entorhinal cortex and parietal cortex. ATP diphosphohydrolase activity presented a decrease (33%) in hippocampal synaptosomes of rats sacrificed 180 min after training. Our results also showed a decrease in synaptosomal ATP diphosphohydrolase (30% and 42% for ATP and ADP, respectively) in entorhinal cortex immediately after training. These findings suggest an integrated action of ATP diphosphohydrolase from hippocampus and entorhinal cortex in the formation of inhibitory avoidance memory.

Animals↗
PubMed2000

(+/-)-Alpha-methyl-4-carboxyphenylglycine, a metabotropic glutamate receptor blocker, impairs retention of an inhibitory avoidance task in rats when infused into the basolateral nucleus of the amygdala.

The amygdala is important for memory processes of emotionally motivated learning and the amygdala glutamatergic system may play a key role in this process. In this study we assessed the effect of the infusion of (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG), a metabotropic glutamate receptor (mGluR) antagonist, into the basolateral complex of the amygdala (BLA) on the learning and retention of an emotionally motivated task. Rats received either vehicle or three different doses of MCPG (0.2, or 1.0, or 5.0 microg/0.2 microl/side, respectively) bilaterally into the BLA, 5 min before they were trained in a continuous multiple-trial inhibitory avoidance (CMIA) task. Response latencies during the training were recorded. Retention was assessed 8 days later. MCPG in the doses given did not significantly affect the acquisition of the CMIA task. However, MCPG at a dose of 5.0 microg/0.2 microl/side impaired the long-term retention test performance. Additionally, a nociception test indicated that dose of MCPG infused into the BLA did not affect the footshock sensitivity. Our results indicate that MCPG, when infused into the BLA of rats prior to the training, impaired long-term memory of aversive training without affecting acquisition.

Amygdala↗
PubMed2000

Time-dependent impairment of inhibitory avoidance retention in rats by posttraining infusion of a mitogen-activated protein kinase kinase inhibitor into cortical and limbic structures.

Mitogen-activated protein kinase (MAPK) is abundantly expressed in postmitotic neurons of the developed nervous system. MAPK is activated and required for induction of long-term potentiation (LTP) in the CA1 area of the hippocampus, which is blocked by the specific inhibitor of the MAPK kinase, PD 098059. Recently it was demonstrated that MAPK is activated in the hippocampus after training and is necessary for contextual fear conditioning learning. The present work tests the role of the MAPK cascade in step-down inhibitory avoidance (IA) retention. PD 098059 (50 microM) was bilaterally injected (0.5 microl/side) into the CA1 region of the dorsal hippocampus or entorhinal cortex at 0, 90, 180, or 360 min, or into the amygdala or parietal cortex at 0, 180, or 360 min after IA training in rats using a 0.4-mA foot shock. Retention testing was carried out 24 h after training. PD 098059 impaired retention when injected into the dorsal hippocampus at 180 min, but not 0, 90, and 360 min after training. When infused into the entorhinal cortex, PD 098059 was amnestic at 0 and 180 min, but not at 90 and 360 min after training. The MAPKK inhibitor also impairs IA retention when infused into the parietal cortex immediately after training, but not at 180 or 360 min. Infusions performed into amygdala were amnestic at 180 min, but not at 0 and 360 min after training. Our results suggest a time-dependent involvement of the MAPK cascade in the posttraining memory processing of IA; the time dependency is different in the hippocampus, amygdala, entorhinal cortex, or parietal cortex of rats.

Amygdala↗
PubMed2000

NMDA receptor antagonism in the basolateral amygdala blocks enhancement of inhibitory avoidance learning in previously trained rats.

Extensive evidence suggests that N-methyl-D-aspartate (NMDA) glutamate receptor channels in the amygdala are involved in fear-motivated learning, and infusion of NMDA receptor antagonists into the amygdala blocks memory of fear-motivated tasks. Recent studies have shown that previous training can prevent the amnestic effects of NMDA receptor antagonists on spatial learning. In the present study, we evaluated whether infusion of the NMDA antagonist D,L-2-amino-5-phosphonopentanoic acid (AP5) into the basolateral nucleus of the amygdala (BLA) impairs reinforcement of inhibitory avoidance learning in rats given previous training. Adult male Wistar rats (220-310 g) were bilaterally implanted under thionembutal anesthesia (30 mg/kg, i.p.) with 9.0-mm guide cannulae aimed 1.0 mm above the BLA. Infusion of AP5 (5.0 microg) 10 min prior to training in a step-down inhibitory avoidance task (0.4 mA footshock) blocked retention measured 24 h after training. When infused 10 min prior to a second training session in animals given previous training (0.2 mA footshock), AP5 blocked the enhancement of retention induced by the second training. Control experiments showed that the effects were not due to alterations in motor activity or footshock sensitivity. The results suggest that NMDA receptors in the basolateral amygdala are involved in both formation of memory for inhibitory avoidance and enhancement of retention in rats given previous training.

2-Amino-5-phosphonovalerate↗
PubMed2000

Time-dependent enhancement of inhibitory avoidance retention and MAPK activation by post-training infusion of nerve growth factor into CA1 region of hippocampus of adult rats.

Several studies have demonstrated that chronic intracerebroventricular nerve growth factor (NGF) infusion has a beneficial effect on cognitive performance of lesioned as well as old and developing animals. Here we investigate: (i) the effect of post-training infusion of NGF into the CA1 region of hippocampus on inhibitory avoidance (IA) retention in rats; (ii) the extension of the effect, in time and space, of NGF infusion into CA1 on the activity of mitogen-activated protein kinase (MAPK, syn: ERK1/2, p42/p44 MAPK). NGF was bilaterally injected into the CA1 regions of the dorsal hippocampus (0.05, 0.5 or 5.0 ng diluted in 0.5 microL of saline per side ) at 0, 120 or 360 min after IA training in rats. Retention testing was carried out 24 h after training. The injection of 5.0 and 0.5, but not 0.05, ng per side of NGF at 0 and 120 min after IA training enhanced IA retention. The highest dose used was ineffective when injected 360 min after training. The infusion of 0. 5 microL of NGF (5.0 ng) induced a significant enhancement of MAPK activity in hippocampal microslices; this enhancement was restricted to a volume with 0.8 mm radius at 30 min after injection. The MAPK activation was still seen 180 min after NGF infusion, although this value showed only a tendency. In conclusion, localized infusion of NGF into the CA1 region enhanced MAPK activity, restricted in time and space, and enhanced IA retention in a time- and dose-dependent manner.

Age Factors↗
PubMed2000

Effect of inhibitory avoidance training on [3H]-glutamate binding in the hippocampus and parietal cortex of rats.

Glutamate receptors have been implicated in memory formation. The aim of the present study was to determine the effect of inhibitory avoidance training on specific [3H]-glutamate binding to membranes obtained from the hippocampus or parietal cortex of rats. Adult male Wistar rats were trained (0.5-mA footshock) in a step-down inhibitory avoidance task and were sacrificed 0, 5, 15 or 60 min after training. Hippocampus and parietal cortex were dissected and membranes were prepared and incubated with 350 nM [3H]-glutamate (N = 4-6 per group). Inhibitory avoidance training induced a 29% increase in glutamate binding in hippocampal membranes obtained from rats sacrificed at 5 min (P<0.01), but not at 0, 15, or 60 min after training, and did not affect glutamate binding in membranes obtained from the parietal cortex. These results are consistent with previous evidence for the involvement of glutamatergic synaptic modification in the hippocampus in the early steps of memory formation.

Analysis of Variance↗
PubMed2000

Infusions of AP5 into the basolateral amygdala impair the formation, but not the expression, of step-down inhibitory avoidance.

We evaluated the effects of infusions of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP5) into the basolateral nucleus of the amygdala (BLA) on the formation and expression of memory for inhibitory avoidance. Adult male Wistar rats (215-300 g) were implanted under thionembutal anesthesia (30 mg/kg, ip) with 9.0-mm guide cannulae aimed 1.0 mm above the BLA. Bilateral infusions of AP5 (5.0 microg) were given 10 min prior to training, immediately after training, or 10 min prior to testing in a step-down inhibitory avoidance task (0.3 mA footshock, 24-h interval between training and the retention test session). Both pre- and post-training infusions of AP5 blocked retention test performance. When given prior to the test, AP5 did not affect retention. AP5 did not affect training performance, and a control experiment showed that the impairing effects were not due to alterations in footshock sensitivity. The results suggest that NMDA receptor activation in the BLA is involved in the formation, but not the expression, of memory for inhibitory avoidance in rats. However, the results do not necessarily imply that the role of NMDA receptors in the BLA is to mediate long-term storage of fear-motivated memory within the amygdala.

2-Amino-5-phosphonovalerate↗
PubMed1999

Dose-dependent impairment of inhibitory avoidance retention in rats by immediate post-training infusion of a mitogen-activated protein kinase kinase inhibitor into cortical structures.

Mitogen-activated protein kinase (MAPK) is a serine/threonine protein kinase abundantly expressed in postmitotic neurons of the developed nervous system. MAPK is activated in and required for both the induction of long-term potentiation (LTP) in hippocampal slices and the acquisition of fear conditioning training in rats. The present work was performed in order to test the effect of the specific inhibitor of MAPK kinase (MAPKK), PD 098059, on retention of a step-down inhibitory avoidance (IA). Adult male Wistar rats were bilaterally injected (0.5 microl/side) with PD 098059 (at 0.5, 5, or 50 microM) or vehicle into the entorhinal cortex or into the parietal cortex immediately after IA training using a 0.4 mA footshock. Retention testing was carried out 24 h after training. PD 098059 impaired retention when injected into the entorhinal cortex at the dose of 50 microM, but not at the doses of 5 or 0.5 microM. When infused into the parietal cortex, PD 098059 was amnestic at the doses of 5 and 50 microM. The drug had no effect when infused at the highest dose in either structure 6 h after training. Our results suggest that the MAPKK inhibitor impairs IA retention memory in a dose-dependent manner when injected immediately after training into entorhinal cortex or parietal cortex. The effective dose is variable according to the neocortical structure studied.

Animals↗
PubMed1999

Normal inhibitory avoidance learning and anxiety, but increased locomotor activity in mice devoid of PrP(C).

Prions are the causative agents of transmissible spongiform encephalopathies. The transmissible agent (PrP(Sc)) is an abnormal form of PrP(C), a normal neuronal protein. The physiological role of PrP(C) remains unclear. In the present report, we evaluated behavioral parameters in Prnp(0/0) mice devoid of PrP(C). Prnp(0/0) mice showed normal short- and long-term retention of a step-down inhibitory avoidance task and normal behavior in an elevated plus maze test of anxiety. During a 5-min exploration of an open field, Prnp(0/0) mice showed normal number of rearings, defecation, and latency to initiate locomotion, but a significant increase in the number of crossings. The results suggest that Prnp(0/0) mice show normal fear-motivated memory, anxiety and exploratory behavior, and a slight increase in locomotor activity during exploration of a novel environment.

Animals↗
PubMed1999

Differential effects of post-training muscimol and AP5 infusions into different regions of the cingulate cortex on retention for inhibitory avoidance in rats.

Adult male Wistar rats were bilaterally implanted with indwelling cannulae in four different coordinates of the cingulate cortex: (1) the anterior cingulate (AC), (2) the rostral region of the posterior cingulate (RC), (3) the upper portion of the caudal region of the posterior cingulate (UC), and (4) the lower portion of the caudal region of the posterior cingulate (LC). After recovery, animals were trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA foot shock). Either immediately, or 90 or 180 min after training, animals received a 0.5-microl infusion of vehicle (phosphate buffer, pH 7.4), of muscimol (0.5 microg), or of AP5 (5.0 microg). Retention testing was carried out 24 h after training. Muscimol was amnestic when given into any of the three coordinates of the posterior cingulate cortex 90 min after training, and when given into LC immediately post-training. In addition, AP5 was amnestic when given into UC 90 min post-training, but not when given into any other region and/or at any other time. None of the treatments had any effect when given into AC. The results suggest that memory processing of the inhibitory avoidance task is regulated by the posterior but not by the anterior cingulate cortex, through muscimol-sensitive synapses, relatively late after training. AP5-sensitive synapses appear to play a very limited role in these processes, restricted to UC.

2-Amino-5-phosphonovalerate↗
PubMed1999

Memory-enhancing treatments do not reverse the impairment of inhibitory avoidance retention induced by NMDA receptor blockade.

The aim of the present research was to verify whether the impairment of retention induced by the N-methyl-d-aspartate (NMDA) receptor blocker (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cycloheptene-5,10 imine (MK-801) can be reversed by memory-enhancing treatments. Adult female Wistar rats were trained and tested in a step-down inhibitory avoidance task (0.3-mA foot shock, 24-h training-test interval). Animals were given an ip injection of saline (SAL) or MK-801 (0.0625 mg/kg) 30 minutes before training, and an ip injection of SAL, epinephrine (EPI) (25 microg/kg), the opioid receptor antagonist naloxone (NAL) (0.4 mg/kg), the glucocorticoid receptor agonist dexamethasone (DEX) (0.3 mg/kg), or glucose (GLU) (320 mg/kg) immediately after training. There was an impairment of inhibitory avoidance retention in the MK-801-SAL, MK-801-EPI, MK-801-NAL, MK-801-DEX, and MK-801-GLU groups. There was an enhancement of retention in the SAL-EPI, SAL-NAL, SAL-DEX, and SAL-GLU groups. A control experiment showed that the amnestic effects of MK-801 could not be attributed to decreased reactivity to the foot shock. The results suggest that memory-enhancing treatments directed at modulatory mechanisms do not reverse the memory impairment induced by NMDA receptor blockade.

Animals↗
PubMed1999

Effects of suramin on hippocampal apyrase activity and inhibitory avoidance learning of rats.

The action of suramin on apyrase activity in hippocampal synaptosomes and its effects on retention of inhibitory avoidance learning were evaluated. Suramin, a P2-purinoceptor antagonist, significantly inhibited in a noncompetitive manner the ATP and ADP hydrolysis promoted by apyrase in hippocampal synaptosomes of adult rats. The Ki values obtained were 72.8 and 109 microM for ATP and ADP hydrolysis, respectively. Intrahippocampal infusion of suramin (0.01, 0.1, 1, and 10 microg) immediately posttraining, in a dose-dependent effect, significantly reduced the response latency during the retention test applied 24 h after the rats received step-down inhibitory avoidance training. The amnesic effects promoted by suramin probably occur by its antagonist action on hippocampal P2-purinoceptors and NMDA receptors. In view of the fact that ATP-metabolizing enzymes and P2-purinoceptors have similar binding domains, these results suggest that suramin can either alter ATP degradation and/or block purinergic neurotransmission.

Adenosine Triphosphate↗
PubMed1999

MAPK and memory.

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Animals↗
PubMed1999

Effects of post-training infusions of a mitogen-activated protein kinase kinase inhibitor into the hippocampus or entorhinal cortex on short- and long-term retention of inhibitory avoidance.

We recently demonstrated the time-dependent impairment of long-term retention of a step-down inhibitory avoidance task in rats induced by post-training infusion of the specific MAPKK (mitogen-activated protein kinase kinase) inhibitor PD 098059 into the hippocampus (HIP), amygdala (AMY), entorhinal cortex (EC) and posterior parietal cortex (PPC). Here we investigate the role of the MAPK cascade in the HIP and the EC on both short- and long-term retention of inhibitory avoidance in rats, using three different doses of the MAPKK inhibitor PD 098059. Adult male Wistar rats were trained and tested in inhibitory avoidance and given an infusion of PD 098059 (0.5, 5.0 or 50.0 microM) at 0, 30, 90, 120, 180, 270 or 360 min after training. A retention test session was carried out at 90, 180 or 270 min after training (short-term memory, STM) and/ or 24 h after training (long-term memory, LTM). When infused into the HIP at 0 min, but not at 30, 90, 120 or 180 min after training, PD 098059 impaired STM. Intrahippocampal PD 098059 impaired LTM when infused at 180 min, but not at 0, 30, 90, 120 or 270 min after training. When infused into the EC, PD 098059 enhanced STM when given at 0 min after training and had no effect when given at 30, 90, 120 or 180 min after training. In this structure, PD 098059 impaired LTM when given at 180 or 270 min, but not at 30, 90, 120 or 360 min after training. All effects were dose-dependent. These findings indicate that the MAPK cascade in the HIP and EC is differentially involved in short- and long-term retention of inhibitory avoidance in rats.

Animals↗
PubMed1999

Increased sensitivity to seizures in mice lacking cellular prion protein.

PURPOSE: The physiologic role of the cellular prion protein (PrPc) is unknown. Mice devoid of PrPc develop normally and show only minor deficits. However, electrophysiologic and histologic alterations found in these mice suggest a possible role for PrPc in seizure threshold and/or epilepsy. METHODS: We tested the sensitivity of PrPc knockout mice to seizures induced by single convulsant or repeated subconvulsant (kindling) doses of pentylenetetrazol (PTZ), and to status epilepticus (SE) induced by kainic acid or pilocarpine. RESULTS: In PTZ kindling, seizure severity progressed faster in the PrPc knockout group, in which 92.8% reached stage 5 or death after 4 days of stimulation, as opposed to 38.4% in wild-type animals. After 10 injections, mortality was 85.7% among knockouts and 15.3% among controls. After a single PTZ injection (60 mg/kg), overall mortality due to seizures was 91% in knockout mice, but only 33% among wild-type animals. Pilocarpine-induced SE (320 mg/kg) caused an 86.7% mortality in knockouts, as opposed to 40% in wild-type animals. Finally, after kainic acid injections (10 mg/kg), 70% of the knockouts developed at least one severe seizure, and 50% showed repetitive seizures, whereas no wild-type animal exhibited observable seizures. CONCLUSIONS: Animals lacking cellular prion protein expression are more susceptible to seizures induced by various convulsant agents. This is perhaps the most striking alteration yet found in PrPc-null mice, who at first analysis appeared to be completely normal. A possible role for PrPc in chronic and idiopathic (familial), secondary, or cryptogenic epilepsies in humans remains to be investigated.

Animals↗