Biomedical subjects

M R Vianna

Publications and source records attributed to M R Vianna.

At least 19 recordsLinked to original sources

PubMed2006

Performance of the DNA-Citoliq liquid-based cytology system compared with conventional smears.

OBJECTIVE: To evaluate the performance of a new, manual, simplified liquid-based system, DNA-Citoliq (Digene Brasil), employed under routine conditions as compared to conventional smears collected from six collaborating private laboratories. METHODS: A panel of cytopathologists, who served as the gold standard diagnosis, adjudicated discordant opinions. RESULTS: Of 3206 pairs of slides considered valid for comparison, there were 3008 in full agreement (93.8%), 112 (3.5%) with one diagnostic category discrepancies, and 86 (2.7%) discordant cases. Among the 288 borderline+ by either method, DNA-Citoliq detected abnormalities in 243 (84.4%), and conventional smears (CS) detected abnormalities in 178 (61.8%) (McNemar test, P < 0.000), a 36.5% increased detection of borderline+ cases. CONCLUSIONS: For mild dyskaryosis, DNA-Citoliq detected 176 cases and CS 125 cases (McNemar test, P < 0.000); and for moderate+severe dyskaryosis 66 versus 32 cases respectively (McNemar test, P < 0.000).

Carcinoma, Squamous Cell↗

PubMed2001

Memory deficits in adult rats following postnatal iron administration.

Two experiments investigated the effects of Fe(2+), administered postnatally to rat pups on days 10-12, upon tests of memory performance and motor behaviour. In experiment I, Wistar rat pups were administered Fe(2+) at doses of either 2.5, 7.5, 15.0 or 30.0 mg/kg, or vehicle, postnatally, and tested in the open-field at 3 months of age, followed 6 weeks later by testing in the radial arm maze. In the open-field test, only the 30.0 mg/kg Fe(2+) group showed a significantly decreased number of ambulations, but not rearings. In the radial arm maze, all four dose groups, demonstrated deficits in acquisition performance from test days 3 to 5. Retention quotients confirmed the cognitive deficits over all four Fe(2+) groups. In experiment II, rats were administered either 2.5, 7.5 or 22.5 mg Fe(2+) per kg, or vehicle, postnatally, and tested in the inhibitory avoidance (IA) conditioning and retention test at 3 months of age. In the IA conditioning test, groups were either given five 10-min preexposures to the test chamber (preexposed) or simply moved to another cage (non-preexposed). IA retention was blocked in non-preexposed rats administered 7.5 and 22.5 mg Fe(2+) per kg whereas in preexposed rats the 7.5 mg/kg group did not differ from the control (vehicle) group, although the preexposed control group showed significantly better retention than the non-preexposed control group. Postnatal iron administration appears to induce long-lasting detrimental effects upon performance of both appetitively and negatively reinforced tests of memory. Analysis of iron content indicated significant increases in the substantia nigra of the 7.5, 15.0 and 30.0 mg/kg dose groups, but not in the 2.5 mg/kg dose group. Postnatal iron administration appears to induce far-reaching effects upon the performance of certain learned behaviours.

Administration, Oral↗

PubMed2001

Retrieval of memory for fear-motivated training initiates extinction requiring protein synthesis in the rat hippocampus.

Evidence that protein synthesis inhibitors induce amnesia in a variety of species and learning paradigms indicates that the consolidation of newly acquired information into stable memories requires the synthesis of new proteins. Because extinction of a response also requires acquisition of new information, extinction, like original learning, would be expected to require protein synthesis. The present experiments examined the involvement of protein synthesis in the hippocampus in the extinction of a learned fear-based response known to involve the hippocampus. Rats were trained in a one-trial inhibitory avoidance task in which they received footshock after stepping from a small platform to a grid floor. They were then given daily retention tests without footshock. The inhibitory response (e.g., remaining on the platform) gradually extinguished with repeated testing over several days. Footshock administered in a different context, instead of a retention test, prevented the extinction. Infusions of the protein synthesis inhibitor anisomycin (80 microg) into the CA1 region of the hippocampus (bilaterally) 10 min before inhibitory avoidance training impaired retention on all subsequent tests. Anisomycin infused into the hippocampus immediately after the 1st retention test blocked extinction of the response. Infusions administered before the 1st retention test induced a temporary (i.e., 1 day) reduction in retention performance and blocked subsequent extinction. These findings are consistent with other evidence that anisomycin blocks both the consolidation of original learning and extinction.

Animals↗

PubMed2001

Facilitation and inhibition of retrieval in two aversive tasks in rats by intrahippocampal infusion of agonists of specific glutamate metabotropic receptor subtypes.

RATIONALE: The generic antagonist of glutamate metabotropic receptors (mGlus), MCPG, blocks retrieval of inhibitory avoidance when infused into the CA1 area of rat hippocampus. It was considered important to study the effect of agonists of different types of mGlus on retrieval both of this task and of a related one, contextual fear. OBJECTIVES: To measure the effect of three mGlu agonists (3HPG, which is selective to mGlu1; LCCG, which binds to mGlu2 and mGlu3; and LAP-4, which binds to mGlu4 and mGlu6), infused bilaterally into CA1, on the retrieval of one-trial inhibitory avoidance and contextual fear in rats. METHODS: Rats bilaterally implanted with cannulae in the CA1 region of the dorsal hippocampus were trained in one-trial step-down inhibitory avoidance or in a contextual fear task and tested for retention 24 h later. The drugs 3HPG, LCCG and LAP-4 were infused into CA1 at different concentration levels 10 min before retention testing. In addition, we studied the effect of these drugs on locomotor and exploratory activity measured in an open field, and on pro- and anti-conflict behaviour in an elevated plus-maze. RESULTS: 3HPG hindered, and LCCG and LAP-4 enhanced, retrieval of the two tasks. In all cases the effects were dose-dependent. The drugs had no effects on open field or plus maze behaviour. CONCLUSIONS: Retrieval of one-trial inhibitory avoidance and of contextual fear is regulated by mGlus in the CA1area of the rat hippocampus. The results suggest that mGlu2s, mGlu3s, mGlu4s and mGlu6s are necessary for retrieval and that mGlu1s play an inhibitory role. The effects are not explainable by nonspecific influences on locomotor or exploratory activity or anxiety levels.

Amino Acids, Dicarboxylic↗

PubMed2001

Novelty enhances retrieval: molecular mechanisms involved in rat hippocampus.

Rats exposed to a novel environment just prior to or 1-2 h, but not 4 or 6 h, before retention testing exhibited an enhanced retrieval of a one-trial inhibitory avoidance training. The bilateral intrahippocampal infusion of PD098059, an inhibitor of mitogen-activated protein kinase (MAPK), the specific upstream activator of p42 and p44 MAPKs, given 10 min before the exposure to the novel environment, blocked the enhancing effect of novelty on memory retrieval. In addition, prenovelty infusion of DL-2-amino-5-phosphonovalerate (APV), an antagonist of glutamate NMDA receptors, produced similar effects. The exposure to the novel environment is associated with an activation of p42 and p44 MAPKs and an increase in the phosphorylation state of the transcription factor cAMP response element binding protein (CREB). No changes were observed in cAMP-dependent protein kinase (PKA) activity or in alpha-CAMKII activation. Taken together, our results indicate that novelty activates hippocampal MAPKs, which are necessary, along with glutamate NMDA receptors, for the enhancing effect of novelty on retrieval.

Animals↗

PubMed2001

The ubiquitin-proteasome cascade is required for mammalian long-term memory formation.

It has been recently demonstrated that ubiquitin-proteasome-mediated proteolysis is required for long-term synaptic facilitation in Aplysia. Here we show that the hippocampal blockade of this proteolytic pathway is also required for the formation of long-term memory in the rat. Bilateral infusion of lactacystin, a specific proteasome inhibitor, to the CA1 region caused full retrograde amnesia for a one-trial inhibitory avoidance learning when given 1, 4 or 7h, but not 10 h, after training. Proteasome inhibitor I produced similar effects. In addition, inhibitory avoidance training resulted in an increased ubiquitination and 26S proteasome proteolytic activity and a decrease in the levels of IkappaB, a substrate of the ubiquitin-proteasome cascade, in hippocampus 4 h after training. Together, these findings indicate that the ubiquitin-proteasome cascade is crucial for the establishment of LTM in the behaving animal.

Amnesia, Retrograde↗

PubMed2001

Chronic treatment with clozapine, but not haloperidol, increases striatal ecto-5'-nucleotidase activity in rats.

In the search for differential mechanisms underlying clozapine's superior antipsychotic efficacy, the purinergic system has been considered, since an antagonist of the adenosine receptor A(2A) was shown to block clozapine acute effects on c-fos expression in rat striatum. Further investigating the interaction of clozapine with the purinergic system, we studied the effects of chronic treatment (28 days, intraperitoneal) with clozapine (25 mg/kg) and haloperidol (1.5 mg/kg) on the activity of ectonucleotidases in the striatum and hippocampus of rats. Clozapine selectively increased striatal 5'-nucleotidase activity (22%) compared to control and haloperidol groups. In vitro, neither drug affected enzyme activities. These results reinforce the differential effects of clozapine compared to haloperidol on the purinergic system.

5'-Nucleotidase↗

PubMed2001

Pharmacological differences between memory consolidation of habituation to an open field and inhibitory avoidance learning.

Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or the entorhinal cortex were submitted to either a one-trial inhibitory avoidance task, or to 5 min of habituation to an open field. Immediately after training, they received intrahippocampal or intraentorhinal 0.5-microl infusions of saline, of a vehicle (2% dimethylsulfoxide in saline), of the glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphono pentanoic acid (AP5), of the protein kinase A inhibitor Rp-cAMPs (0.5 microg/side), of the calcium-calmodulin protein kinase II inhibitor KN-62, of the dopaminergic D1 antagonist SCH23390, or of the mitogen-activated protein kinase kinase inhibitor PD098059. Animals were tested in each task 24 h after training. Intrahippocampal KN-62 was amnestic for habituation; none of the other treatments had any effect on the retention of this task. In contrast, all of them strongly affected memory of the avoidance task. Intrahippocampal Rp-cAMPs, KN-62 and AP5, and intraentorhinal Rp-cAMPs, KN-62, PD098059 and SCH23390 caused retrograde amnesia. In view of the known actions of the treatments used, the present findings point to important biochemical differences in memory consolidation processes of the two tasks.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

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

Pharmacological demonstration of the differential involvement of protein kinase C isoforms in short- and long-term memory formation and retrieval of one-trial avoidance in rats.

RATIONALE: The hippocampal protein kinase C (PKC) family is involved in the early events of consolidation of long-term potentiation (LTP) and long-term memory (LTM). Results so far are indecisive about which PKC isoform is involved and as to whether any of them plays a role in short-term memory (STM) processes, which have recently been shown to be separate from those of LTM in the hippocampus-dependent one-trial step-down inhibitory avoidance task. OBJECTIVES: To measure the effect of two PKC inhibitors, one (Gö 6976) selective to the calcium-dependent isoforms alpha and beta I, and the other (Gö 7874) unspecific as to PKC isoforms on the formation and retrieval of STM and LTM of one-trial inhibitory avoidance. METHODS: Rats bilaterally implanted with cannulae in the CA1 region of the dorsal hippocampus were trained in one-trial step-down inhibitory avoidance. The effect of these two drugs on STM and LTM formation was investigated as follows. Animals were infused 10 min before or 50, 110, or 170 min after inhibitory avoidance training with a vehicle (2% dimethylsulfoxide in saline), or with Gö 6976 (0.92 nM or 4.6 nM) or Gö 7874 (1.96 nM or 8 nM) dissolved in the vehicle. Infusion volume was 0.5 microliter in all cases. Animals were tested 1.5 h and 3 h after training for STM and at 24 h for LTM. In order to study the effects of these compounds on retrieval, they were infused into the hippocampus 10 min prior to STM testing at 3 h (see above) or 10 min before LTM testing at 24 h. In addition, the effect of Gö 6976 and Gö 7874 was studied on general activity measured in an open field, and on performance in an elevated plus maze. RESULTS: STM was suppressed by 4.6 nM Gö 6976 given 10 min before or 50 min after training. LTM was cancelled by the higher dose of the two compounds given 10 min before, or 50 min or 110 min after training. None of the two compounds infused 170 min post-training affected the retrieval of STM measured 10 min later. However, both compounds given 10 min before testing inhibited the retrieval of LTM measured at 24 h. This effect cannot be attributed to influences on locomotor activity or anxiety levels, since the drugs had no effect on performance in the open field but were mildly "anxiogenic" (pro-conflict) and reduced the number of entries into open and closed arms and rearings. CONCLUSIONS: LTM consolidation requires in part alpha- and/or beta 1-PKC and in part other PKC isoforms. STM formation requires instead only alpha and/or beta I-PKC and during a more limited period of time. In addition, PKC appears not to be necessary for the retrieval of STM, but is crucial for the retrieval of LTM. These findings further point to a biochemical separation of STM and LTM, as ascertained in numerous previous studies.

Animals↗

PubMed2000

Involvement of the medial precentral prefrontal cortex in memory consolidation for inhibitory avoidance learning in rats.

Adult male Wistar rats were trained in a step-down inhibitory avoidance learning task (3.0-s, 0.4-mA foot shock), received a 0.5-microl infusion of muscimol (0.02, 0.1, or 0.5 microg), AP5 (0.16, 0.34, 0. 5, 1.6, or 5.0 microg), SCH 23390 (0.05, 0.34, 0.5, or 1.75 microg), saline, or vehicle (DMSO 20%) into the anterior medial precentral area (Fr2) (CI) immediately after training, and were tested 24 h later. Muscimol (0.02, 0.1, or 0.5 microg), AP5 (0.34 or 0.5 microg), or SCH (0.5 or 1.75 microg) were amnesic. Then, animals were infused with muscimol (0.1 or 0.5 microg), AP5 (0.34, 0.5, or 5.0 microg), or SCH (0.5 microg) at other posttraining times and/or into the junction of Fr1-Fr2 (CII). Muscimol (0.1 and 0.5 microg) or SCH into CI were amnesic when given 90 or 180 min after training, but not when given 270 min after training. Muscimol (0.5 microg, but not 0.1 microg) or SCH into CII were amnesic when given 90 min after training, but not when given 0 or 180 min after training. AP5 (0.5, but not 5.0 microg) was amnesic when given into CI, but not into CII, at 0 or 180 min posttraining, and a trend toward an amnesic effect was seen at 90 min posttraining. The results suggest that 1) the glutamatergic, GABAergic, and dopaminergic systems in Fr2 are involved in the consolidation of memory for inhibitory avoidance learning, either directly or as parts of modulatory systems; and 2) timing of involvement of anterior Fr2 (CI) is different from that of posterior Fr2 (CII).

2-Amino-5-phosphonovalerate↗

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

Differential role of hippocampal cAMP-dependent protein kinase in short- and long-term memory.

One-trial step-down inhibitory (passive) avoidance training is followed by two peaks of cAMP-dependent protein kinase (PKA) activity in rat CA1: one immediately after training and the other 3 h later. The second peak relies on the first: Immediate posttraining infusion into CA1 of the inhibitor of the regulatory subunit of PKA, Rp-cAMPS, at a dose that reduces PKA activity during less than 90 min, cancelled both peaks. Long-term memory (LTM) of this task measured at 24 h depends on the two peaks: Rp-cAMPS given into CA1 0 or 175 min posttraining, but not between those times, blocked LTM. However, the effect of immediate posttraining Rp-cAMPS on LTM could not be reversed by the activator of the regulatory subunit of PKA, Sp-cAMPS, given at 180 min, which suggests that, for LTM, the first peak may be more important than the second. When given at 0, 22, 45, or 90, but not at 175 min from training, Rp-cAMPS blocked short-term memory (STM) measured at 90 or 180 min. This effect of immediate posttraining Rp-cAMPS infusion on STM but not that on LTM was readily reversed by Sp-cAMPS infused 22 min later. On its own, Sp-cAMPS had effects exactly opposite to those of the inhibitor. It enhanced LTM when given at 0 or 175 min from training, and it enhanced STM when given at 0, 22, 45, or 90 min from training. These findings show that STM and LTM formation require separate PKA-dependent processes in CA1. STM relies on the continued activity of the enzyme during the first 90 min. LTM relies on the two peaks of PKA activity that occur immediately and 180 min posttraining.

Animals↗

PubMed2000

The anticonvulsant compound gabapentin possesses anxiolytic but not amnesic effects in rats.

This report describes the effects of the antiepileptic agent gabapentin on anxiety and memory. Male Wistar rats received intraperitoneal administrations of gabapentin (10, 30 and 100mg/kg), diazepam (1 mg/kg), saline or diazepam vehicle 30 minutes prior to experimental procedures. Animals were: (1) tested on step-down inhibitory avoidance (footshock 0.3 mA) and habituation to an open-field for memory assessment; and (2) submitted to the elevated plus-maze to evaluate the potential anxiolytic effects of gabapentin. Animals treated with gabapentin showed a reduction in anxiety similar to that observed in animals treated with diazepam. Memory was not affected by gabapentin in any of the tests, but was impaired by diazepam. The lack of effects of gabapentin on memory suggest a potential advantage of this drug over compounds with previously known anxiolytic property, which have amnesic effects at doses used for the treatment of anxiety disorders.

Acetates↗

PubMed2000

Short- and long-term memory: differential involvement of neurotransmitter systems and signal transduction cascades.

Since William James (1890) first distinguished primary from secondary memory, equivalent to short- and long-term memory, respectively, it has been assumed that short-term memory processes are in charge of cognition while long-term memory is being consolidated. From those days a major question has been whether short-term memory is merely a initial phase of long-term memory, or a separate phenomena. Recent experiments have shown that many treatments with specific molecular actions given into the hippocampus and related brain areas after one-trial avoidance learning can effectively cancel short-term memory without affecting long-term memory formation. This shows that short-term memory and long-term memory involve separate mechanisms and are independently processed. Other treatments, however, influence both memory types similarly, suggesting links between both at the receptor and at the post-receptor level, which should not be surprising as they both deal with nearly the same sensorimotor representations. This review examines recent advances in short- and long-term memory mechanisms based on the effect of intra-hippocampal infusion of drugs acting upon neurotransmitter and signal transduction systems on both memory types.

Animals↗

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

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↗