Consuelo Sancho

Chronic administration of risperidone to healthy rats: A behavioural and morphological study

Taking into account that most of the experimental research into the effects of antipsychotic drugs has mainly focused on behavioural aspects, the aim of the present work is to investigate the effects of a chronic therapeutic dose of risperidone (1 mg/kg/day during 140 days) on both behavioural and morphological aspects in healthy rats. The behavioural results revealed only minor modifications in prepulse inhibition, showing the risperidone-treated group higher values at 70 days of treatment with respect to the vehicle group. Moreover, in the open-field test, this group showed a greater incidence of grooming. In the active avoidance test, no differences were found between the groups studied. Additionally, in the morphological study performed to analyse cortical thickness and the number of GFAP-, CaBP-, PV- and Fos-immunostained cells no differences were seen between the two groups studied. It is important to note that the risperidone-treated group showed a slight increase in the total number of cells counted, although this increase was not significant. Our results indicate that the chronic administration of therapeutic doses of risperidone does not produce any dramatic behavioural or morphological changes in healthy animals.

The effects of sertraline administration from adolescence to adulthood on physiological and emotional development in prenatally stressed rats of both sexes

Sertraline (SERT) is a clinically effective Selective Serotonin Reuptake Inhibitor (SSRI) known to increase and stabilize serotonin levels. This neurotransmitter plays an important role in adolescent brain development in both rodents and humans, and its dysregulation has been correlated with deficits in behavior and emotional regulation. Since prenatal stress may disturb serotoninergic homeostasis, the aim of this study was to examine the long-lasting effects of exposure to SERT throughout adolescence on behavioral and physiological developmental parameters in prenatally stressed Wistar rats. SERT was administered (5 mg/kg/day p.o.) from the age of 1–3 months to half of the progeny, of both sexes, of gestating dams stressed by use of a restraint (PS) or not stressed. Our data reveal that long-term SERT treatment slightly reduced weight gain in both sexes, but reversed the developmental disturbed “catch-up” growth found in PS females. Neither prenatal stress nor SERT treatment induced remarkable alterations in behavior and had no effects on mean startle reflex values. However, a sex-dependent effects of PS was found: in males the PS paradigm slightly increased anxiety-like behavior in the open field, while in females, it impaired startle habituation. In both cases, SERT treatment reversed the phenomena. Additionally, the PS animals exhibited a disturbed leukocyte profile in both sexes, which was reversed by SERT. The present findings are evidence that continuous SERT administration from adolescence through adulthood is safe in rodents and lessens the impact of prenatal stress in rats.

Effects of verapamil and elgodipine on isoprenaline-induced metabolic responses in rabbits

Verapamil (0.17 microg kg(-1) min(-1) intravenous, i.v.) but not elgodipine (35 ng kg(-1) min(-1)) modestly enhanced the weak blood glucose increase induced by the i.v. infusion of isoprenaline (0.3 microg kg(-1) min(-1)) in conscious rabbits. However, elgodipine but not verapamil suppressed the increase in circulating insulin evoked by the agonist. Both drugs enhanced the rise in plasma lactate mediated by isoprenaline but only elgodipine potentiated the lipolytic effect of the agonist. In isolated islets elgodipine (10(-6) M) blocked forskolin (10(-6) M)-induced insulin release. However, in rabbit adipocytes elgodipine potentiated both glycerol release and cAMP accumulation induced by isoprenaline (10(-8)-10(-6) M). Excess K(+) (40-60 mM) did not alter basal lipolysis or the response to isoprenaline in either rabbit or mouse adipocytes. Therefore, Ca2+ influx through L-type Ca2+ channels does not seem to play a significant role in the lipolytic effect of isoprenaline. Metabolic alterations found with Ca2+ channel antagonists were of minor intensity and probably devoid of pathological implications.

Chronic administration of risperidone in a rat model of schizophrenia: A behavioural, morphological and molecular study

In the present work we analyzed the effect of the chronic administration of risperidone (2mg/kg over 65 days) on behavioural, morphological and molecular aspects in an experimental model of schizophrenia obtained by bilateral injection of ibotenic acid into the ventral hippocampus of new-born rats. Our results show that during their adult lives the animals with hippocampal lesions exhibit different alterations, mainly at behavioural level and in the gene expression of dopamine D(2) and 5-HT(2A) receptors. However, at morphological level the study performed on the prefrontal cortex did not reveal any alterations in either the thickness or the number of cells immunoreactive for c-Fos, GFAP, CBP or PV. Overall, risperidone administration elicited a trend towards the recovery of the values previously altered by the hippocampal lesion, approaching the values seen in the animals without lesions. It may be concluded that the administration of risperidone in the schizophrenia model employed helps to improve the altered functions, with no significant negative effects.

No association between prepulse inhibition of the startle reflex and neuropsychological deficit in chronic schizophrenia

Sensorimotor gating deficits are relevant in schizophrenia and can be measured using prepulse inhibition (PPI) of the startle reflex. It is conceivable that such deficits may hinder the cognitive functions in schizophrenia patients. In this study, using PPI and a neuropsychological battery, we studied this possibility in a group of 23 acute, neuroleptic-free schizophrenia patients and 16 controls. A non-significant decrease in PPI was found in the patients as compared to the controls, as well as significant differences in the performance of Trail A and B in Wisconsin Card Sorting and Digit/Symbol Tests. No statistically significant correlations between PPI and neuropsychological performance were found after the correction for multiple comparisons in any group. Our results suggest that PPI deficits in schizophrenia patients may not contribute to the cognitive deficits typical of that illness, at least in patients with a non-significant PPI decrease.

Prepulse inhibition of the startle reflex in schizophrenia remains stable with short-term quetiapine

PURPOSE To study the short-term effect of treatment with quetiapine on prepulse inhibition (PPI) deficits of the startle reflex in schizophrenia patients. SUBJECTS AND METHODS Using PPI, we studied a group of 21 schizophrenia patients and 16 controls. Seventeen of the patients were re-tested with PPI after 21 days of treatment with quetiapine. RESULTS At baseline, an almost significant decrease in PPI was found in the patients as compared to the controls. PPI measurements did not change in the patients after 21 days of treatment with quetiapine, despite their clinical improvement. CONCLUSION Our results suggest that short-term quetiapine treatment may not modify PPI measures in schizophrenia patients.

Relations between Sensorimotor Integration and Speech Disorders in Parkinson's Disease

BACKGROUND Sensorimotor integration mechanisms can be affected by many factors, among which are those involving neuromuscular disorders. Parkinsons disease (PD) is characterized by well-known motor symptoms, among which lately have been included motor speech deficits. Measurement of the acoustic startle reflex (ASR) and its modulations (prepulse inhibition and prepulse facilitation, PPI and PPF respectively) represent a simple and quantifiable tool to assess sensorimotor function. However, it remains unknown whether measures of the PPI and PPF are associated with motor speech deficits in PD. METHODS A total of 88 subjects participated in this study, 52 diagnosed with PD and 36 control subjects. After obtaining written informed consent, participants were assessed with PPI at several interstimulus intervals, and PPF at 1000 ms using the SRH-Lab system (San Diego, CA). Percentage of change in the amplitude and latency of the ASR was analyzed between groups. Voice recordings were register of a specific text given to the subjects with a professional recorder and temporal patterns of speech were analyzed. RESULTS Statistical analysis conducted in this study showed differences in PPI and PPF in subjects with PD compared to controls. In addition, discriminative parameters of voice abnormalities were observed in PD subjects related to control subjects showing a reduction in phonation time, vowel pulses, breaks, breakage and voice speech periods. CONCLUSIONS PD presents a disruption in sensorimotor filter mechanisms and speech disorders, and there is a relationship between these alterations. The correlation between the PPI and PPF with an alteration of the voice in PD subjects contributes toward understanding mechanism underlying the neurophysiological alterations in both processes. Overall, easy and non-invasive tests such as PPI, PPF together with voice analysis may be useful to identify early stages of PD.

Long-Term Sertraline Intake Reverses the Behavioral Changes Induced by Prenatal Stress in Rats in a Sex-Dependent Way

Early life stress is a major factor underlying the vulnerability to respond to stressful events later in life. The present study attempted to evaluate the role of prenatal stress affecting the development of stress-related disorders and their reversion by postnatal exposure to Sertraline (SERT), a front-line medication for medication for posttraumatic stress disorder (PTSD) in humans. To achieve this, adult male and female prenatally stressed (PS) or unstressed (Controls) offspring rats, following oral chronic treatment with SERT (5 mg/kg/day; from 1 month to 4 months old), or not, were studied prior to and after a traumatic event. First, anxiety-like behavior during the prepulse inhibition (PPI) test, a modulation of the startle reflex, was examined in all animals. Subsequently, the animals were subjected to a session of mild inescapable footshocks (IS; 0.35 mA, 5 s) in a shuttle box that was followed by 4 days of situational reminders in the aversive context. Prior to the footshocks no effects of PS or SERT were shown, and no changes in PPI and the habituation to the shuttle box were found. After them, PS led animals to exhibit behavioral alterations. When compared to the Controls, PS animals of both sexes displayed less rearing activity in the aversive environment. PS males responded less to footshock delivery and, in most of the animals, fear extinction was impaired. Moreover, the early postnatal exposure to SERT lessened the behavioral impact of PS in females, while in males it had no effect. Current results extend previous data from our laboratory, showing that PS heightened vulnerability to stress later on, and that SERT acts differently in males and females.

Acquisition of Competencies by Medical Students in Neurological Emergency Simulation Environments Using High Fidelity Patient Simulators

The training of medical students demands practice of skills in scenarios as close as possible to real ones that on one hand ensure acquisition of competencies, and on the other, avoid putting patients at risk. This study shows the practicality of using high definition mannequins (SimMan 3G) in scenarios of first attention in neurological emergencies so that medical students at the Faculty of Medicine of the University of Salamanca could acquire specific and transversal competencies. The repetition of activities in simulation environments significantly facilitates the acquisition of competencies by groups of students (p < 00.5). The greatest achievements refer to skills whereas the competencies that demand greater integration of knowledge seem to need more time or new sessions. This is what happens with the competencies related to the initial diagnosis, the requesting of tests and therapeutic approaches, which demand greater theoretical knowledge.

A simulation environment using a simulator mannequin for the acquisition of skills by medical students in traumatic brain injury

The processes of teaching and learning in the health sciences more than justify the use of new education technologies in which clinical simulation helps students to acquire skills and competencies in scenarios similar to those of the real world, but without involving patients physically. The present contribution aims to explore the characteristics and application of a high-definition simulator in a group of students from the School of Medicine of the University of Salamanca in order for them learn to manage patients with traumatic brain injury in A&E.