Maria Beatriz Cardoso Ferreira

Neurotransmitter receptors involved in post-training memory processing by the amygdala, medial septum, and hippocampus of the rat.

Rats were trained and tested in habituation to a novel environment and step-down inhibitory avoidance. Immediately after training in each task the animals received intra-amygdala, intraseptal, or intrahippocampal micro-injections of agonists and antagonists of various neurotransmitter receptors. In the habitation task, intrahippocampal, but not intra-amygdala or intraseptal administration of the NMDA receptor antagonist aminophosphornopentanoic acid (AP5, 5.0 micrograms) or of the muscarinic receptor antagonist, scopolamine (2.0 micrograms) caused amnesia and the indirect antagonist of GABA-A receptors, picrotoxin (0.08 microgram), caused retrograde facilitation. Intrahippocampal administration of the respective agonists, glutamate, oxotremorine, and muscimol, had effects of their own opposite to those of the blockers, and norepinephrine (0.3 microgram) caused memory facilitation. In the avoidance task, results obtained with drug infusions given into the three structures were very similar: in all cases, AP5, scopolamine, and muscimol were amnestic, and glutamate, oxotremorine, norepinephrine, and picrotoxin caused memory facilitation. In addition, also in the three structures, picrotoxin counteracted the amnestic effect of AP5 and/or scopolamine and the beta-adrenoceptor blocker, timolol (0.3 microgram), while ineffective on its own, attenuated all the effects of picrotoxin. The results suggest that similar synaptic mechanisms in the amygdala, medial septum, and hippocampus are involved in memory consolidation: NMDA, muscarinic, and beta-noradrenergic receptors stimulate and GABA-A receptors inhibit this process, and beta-noradrenergic receptors modulate the GABAergic synapses. In the avoidance task these mechanisms operate in the three structures: in habituation only those in the hippocampus are operative. Possibly in each structure these mechanisms regulate, if not actually consolidate, a different aspect, component, or form of memory.

Risk factors for preoperative anxiety in adults

Background: Patients who undergo surgery experience acute psychological distress in the preoperative period. The objective of this study was to identify and quantify the effect of risk factors for preoperative anxiety in adults.

Preoperative predictors of moderate to intense acute postoperative pain in patients undergoing abdominal surgery

Background:   Pain is a sensory and emotional experience that is influenced by physiologic, sensory, affective, cognitive, socio‐cultural, and behavioral factors. Consistent with the perspective to improve the postoperative pain control, the present study has the purpose of assessing the effect of presurgical clinical factors, psychological and demographic characteristics as predictors for reporting moderate to intense acute postoperative pain.

Amnesia by post-training infusion of glutamate receptor antagonists into the amygdala, hippocampus, and entorhinal cortex

The blockers of glutamate receptors, aminophosphonovaleric acid (AP5) (5.0 micrograms) and cyano-nitroquinoxaline-dione (CNQX) (0.5 microgram), were infused bilaterally into the amygdala, dorsal hippocampus, or entorhinal cortex of rats through indwelling cannulae 0, 90, 180, or 360 min after step-down inhibitory avoidance training. Animals were tested for retention 24 h after training. In the amygdala or hippocampus, AP5 was amnestic when given 0 min after training and CNQX was amnestic when given 0, 90, or 180 min after training. In the entorhinal cortex, AP5 was amnestic when given 90 or 180 min after training and CNQX had no effect. The results suggest that a phenomenon sensitive first to AP5 and then to CNQX in the amygdala and hippocampus, probably long-term potentiation (LTP), is crucial to post-training memory processing. LTP in these two structures could underlie their role in memory consolidation and could explain the late involvement of the entorhinal cortex in post-training memory processing.

Long-lasting delayed hyperalgesia after chronic restraint stress in rats—effect of morphine administration

Different effects upon the nociceptive response have been observed with exposure to acute and chronic stress in rats. In the present study we repeatedly submitted rats to restraint for 40 days, inducing hyperalgesia using the tail-flick test. A new session of acute stress was applied at the end of 40 days period, and the chronically-stressed animals demonstrated analgesia after forced swimming, but not after restraint. The effect of stress interruption for 14 or 28 days on the nociceptive threshold was then investigated. The basal tail-flick latency remained decreased for at least 28 days (hyperalgesic effect). Following the periods of suspension, the animals were submitted to new session of acute restraint, and stress-induced analgesia was observed only after 28 days of stress interruption. Thus, the mechanisms involved in the long-lasting hyperalgesia presented in this study are not exactly the same as those responsible for the analgesia induced by acute stressors. After 40 days of chronic stress treatment, morphine was injected i.p. (1.0, 5.0 mg/kg or saline). The repeatedly stressed rats displayed decreased morphine effects on nociception compared to unstressed controls. The tolerance of the response to morphine agrees with previous studies suggesting that chronic restraint stress could modify the activity of opioid systems.

Risk factors for postoperative anxiety in adults

We identified risk factors for postoperative anxiety and quantified their effect on 712 adults between 18 and 60 years of age (ASA I–III physical status) undergoing elective surgery under general anaesthesia, neural blockade or both. The measuring instruments were a structured questionnaire, a pain visual analogue scale, the McGill Pain Questionnaire, the State‐Trait Anxiety Inventory, the Montgomery–Äsberg Depression Rating Scale, a Self‐Reporting Questionnaire‐20, and a Self‐Perception of Future Questionnaire. Multivariate conditional regression modelling taking into account the hierarchical relationship between risk factors revealed that postoperative anxiety was associated with ASA status III (OR = 1.48), history of smoking (1.62), moderate to intense postoperative pain (OR = 2.62) and high pain rating index (OR = 2.35), minor psychiatric disorders (OR = 1.87), pre‐operative state‐anxiety (OR = 2.65), and negative future perception (OR = 2.20). Neural block anaesthesia (OR = 0.72), systemic multimodal analgesia (OR = 0.62) and neuroaxial opioids with or without local anaesthesia (OR = 0.63) were found to be protective factors against postoperative anxiety.

Differential involvement of hippocampal and amygdalar NMDA receptors in contextual and aversive aspects of inhibitory avoidance memory in rats

Adult male rats bilaterally implanted with guide canullae aimed either at the dorsal hippocampus (dHIP) or the basolateral nucleus of the amygdala (BLA) were trained in a step-down inhibitory avoidance task (IA) and tested for retention 24 h after training. Immediately after training, animals were given a bilateral infusion of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP5) (5.0 microg) into the dHIP or the BLA. Both intrahippocampal and intraamygdala infusions of AP5 blocked IA retention. Preexposure to the training box, but not to a different environment 24 h prior to training prevented the impairing effect of intrahippocampal infusion of AP5 on retention. Preexposure did not affect the retention impairment induced by intraamygdala infusion of AP5. These data suggest that hippocampal NMDA receptors might be involved in the contextual and spatial aspects, while amygdalar NMDA receptors might be involved in the aversive aspects of memory for IA.

Adverse drug reactions: a cohort study in internal medicine units at a university hospital

ObjectivesAdverse drug reactions (ADRs) are important causes of hospitalization, morbidity and mortality in hospitalized patients. In addition to the impact they have on human life, they also significantly influence health costs. This study intended to (1) identify suspected ADRs and establish their frequency of development, (2) establish a causal relationship with the suspected drug(s) and (3) verify if there is an association between the development of an ADR and factors such as age, gender, number of diagnoses and number of prescribed medications.MethodsThis cohort study considered hospitalized patients at five inpatient internal medicine units in a university hospital located in southern Brazil. Patients were intensively monitored in order to identify suspected ADRs during hospitalization. The types of reactions were classified and a causal relationship was established using an algorithm.ResultsThe cohort study followed 333 patients and approximately 43% of them presented at least one suspected ADR. Three hundred and sixty suspected ADRs were identified, with 19.7% manifesting before the patient was admitted and 80.3% during hospitalization. Medications that were most commonly involved in these suspected cases were anti-infectious agents followed by drugs that act on the central nervous system (CNS). The follow-up length and number of medications in use were independent risk factors for the development of an ADR. The same relationship was not observed for age, gender and number of diagnoses.ConclusionADRs are a major problem in our setting and measures must be adopted to minimize them.

Effect of pre-operative anxiolysis on postoperative pain response in patients undergoing total abdominal hysterectomy

Summary In a double blind, placebo‐controlled trial, we have assessed the effects of pre‐operative anxiolysis on postoperative pain scores in 112 ASA I‐II women, aged 18–65 years, scheduled to undergo total abdominal hysterectomy. Subjects were randomly allocated to receive either oral diazepam 10 mg (n=56) or placebo (n=56) pre‐operatively. Postoperative anxiety, pain scores, analgesic consumption, and sedation were evaluated at several time points during the first 24 h following surgery. Postoperative pain scores were found to be significantly higher in the diazepam group. Trait and state anxiety showed a significant effect on pain scores, independent of the treatment group. No difference was found between the groups in morphine consumption, but there was a significant reduction in morphine consumption with time.

Interaction between repeated restraint stress and concomitant midazolam administration on sweet food ingestion in rats

Emotional changes can influence feeding behavior. Previous studies have shown that chronically stressed animals present increased ingestion of sweet food, an effect reversed by a single dose of diazepam administered before testing the animals. The aim of the present study was to evaluate the response of animals chronically treated with midazolam and/or submitted to repeated restraint stress upon the ingestion of sweet food. Male adult Wistar rats were divided into two groups: controls and exposed to restraint 1 h/day, 5 days/week for 40 days. Both groups were subdivided into two other groups treated or not with midazolam (0.06 mg/ml in their drinking water during the 40-day treatment). The animals were placed in a lighted area in the presence of 10 pellets of sweet food (Froot loops). The number of ingested pellets was measured during a period of 3 min, in the presence or absence of fasting. The group chronically treated with midazolam alone presented increased ingestion when compared to control animals (control group: 2.0 +/- 0.44 pellets and midazolam group: 3.60 +/- 0.57 pellets). The group submitted to restraint stress presented an increased ingestion compared to controls (control group: 2.0 +/- 0.44 pellets and stressed group: 4.18 +/- 0.58 pellets). Chronically administered midazolam reduced the ingestion in stressed animals (stressed/water group: 4.18 +/- 0.58 pellets; stressed/midazolam group: 3.2 +/- 0.49 pellets). Thus, repeated stress increases appetite for sweet food independently of hunger and chronic administration of midazolam can decrease this behavioral effect.