Search

Knowing which teaching methods students value the most is important, as it directly affects the quality of learning. This paper analyzes which teaching methods are most commonly used in the Medicine Degree at a Spanish university, as perceived by both professors and students. It further explores the students’ assessments of these methods and the relationship between these assessments and the methods’ frequencies of use. The participants were 36 professors and 150 students. Professors completed the Teaching and Assessment Methodology of University Faculty Questionnaire (TAMUFQ), while students were administered a specially designed questionnaire. The questionnaire defined twelve teaching methods, and students were asked to provide their personal assessment and the frequency of use for each method based on their experiences. Professors reported adhering to a traditional style of teaching and assessment. According to the students, the most commonly used method was the lecture, although their assessments of lectures were significantly lower than the frequency with which that method was being used. Regarding the eleven remaining methods, the prospective doctors’ assessments were significantly higher than the methods’ degree of use. The main conclusion is that, while students did not negatively assess lectures, they considered them to be overused. This may mean that the potential of other teaching methods is being missed.

Cocaine is the most prevalent illegal stimulant drug in Europe among the adult population. Its abuse is characterized by a faster substance abuse disorder (SUD) development than other drugs, with high vulnerability to relapse. However, there does not exist an effective treatment for cocaine dependence. Sex differences have been reported in psychological disorders including SUD. For this reason, it is essential to identify risk factors that predict susceptibility or resilience to cocaine addiction for the development of effective prevention strategies considering sex differences. In the present study, the main objective was to determine more sensitive phenotypes to the conditioned reinforcing effects of cocaine in both sexes. Anxiety-like behavior and the locomotor response to novelty were evaluated in the elevated plus maze, and despair in the tail suspension test, as well as vulnerability traits linked with a high sensitivity to the reinforcing effects of a subthreshold dose of cocaine (1 mg/kg) in the conditioned place preference (CPP) paradigm in male and female mice. Our results indicated that only female mice with high anxiety, low locomotor response to novelty or low despair levels acquired CPP induced by cocaine, while male mice with low anxiety, high locomotor response to novelty or high despair levels presented a higher susceptibility to the rewarding effects of cocaine than others. These sex differences in the results reveal an opposite pattern in males and females on the relationship between anxiety- and depressive-like behaviors and cocaine vulnerability, demonstrating the need to include female mice in preclinical studies.

Prepulse inhibition (PPI) of the startle reflex is a measure of sensory-motor synchronization. A deficit in PPI has been observed in psychiatric patients, especially those with schizophrenia and vulnerable subjects, since the neural bases of this disorder are also involved in the regulation of PPI. Recently, we have reported that baseline PPI levels in mice can predict their sensitivity to the conditioned reinforcing effects of cocaine in the conditioned place preference (CPP) paradigm. Mice with a low PPI presented a lower sensitivity to the conditioned rewarding effects of cocaine; however, once they acquired conditioned preference with a higher dose of the drug, a more persistent associative effect of cocaine with respect to environmental cues was evident in these animals when compared with High-PPI mice. Therefore, we proposed that the PPI paradigm can determine subjects with a higher vulnerability to the effects of cocaine. Developing locomotor sensitization after pre-exposure to cocaine is considered an indicator of transitioning from recreational use to a compulsive consumption of the drug. Thus, the aim of the present study was to evaluate whether subjects with a low PPI display a higher locomotor sensitization induced by cocaine. First, male and female OF1 mice were classified as High- or Low-PPI according to their baseline PPI levels. Subsequently, the motor effects induced by an acute dose of cocaine (Experiments 1 and 2) and the development of locomotor sensitization induced by pre-exposure to this drug (Experiments 3 and 4) were recorded using two apparatuses (Ethovision and actimeter). Low-PPI mice presented low sensitivity to the motor effects of an acute dose of cocaine, but a high increase of activity after repeated administration of the drug, thus suggesting a great developed behavioral sensitization. Differences after pretreatment with cocaine vs. saline were more pronounced among Low-PPI subjects than among High-PPI animals. These results endorse our hypothesis that the PPI paradigm can detect subjects who are more likely to display behaviors induced by cocaine and which can increase the risk of developing a cocaine use disorder. Herein, we further discuss whether a PPI deficit can be considered an endophenotype for cocaine use disorder.

The prepulse inhibition (PPI) of the startle response can identify the rodents that are more sensitive to the effects of cocaine. Mice with a lower PPI presented a higher vulnerability to the effects of cocaine and a higher susceptibility to developing a substance use disorder (SUD). Maternal separation with early weaning (MSEW) is a relevant animal model to induce motivational alterations throughout life. Nevertheless, only a few studies on females exist, even though they are more vulnerable to stress- and cocaine-related problems. Hence, the aim of the present study was to evaluate the ability of PPI to identify females with a greater vulnerability to the long-term consequences of early stress on the motivational effects of cocaine. Female mice underwent MSEW and were classified according to their high or low PPI. They were then assessed in the cocaine-induced locomotor sensitization test, the conditioned place preference paradigm or the operant self-administration paradigm. Additionally, they were also evaluated in the passive avoidance task, the tail-suspension and the splash tests. The results revealed that the females with lower PPI presented higher consequences of MSEW on the effects of cocaine and showed an increase in anhedonia-like behaviours. Our findings support that a PPI deficit could represent a biomarker of vulnerability to the effects of cocaine induced by MSEW.

Un déficit de la inhibición por Prepulso (IPP) de la respuesta de sobresalto es considerado un endofenotipo de la esquizofrenia. El estrés es un factor precipitante de este trastorno y puede alterar los niveles de IPP de los sujetos. El objetivo de este estudio fue comprobar las consecuencias a largo plazo que un estrés repetido provoca en la IPP de los sujetos según su nivel basal, sea alto o bajo. Ratones OF1 (57 machos, 59 hembras) fueron categorizados como altos o bajos según su nivel de IPP. Posteriormente, fueron sometidos a estrés (0, 30 ó 60 minutos de inmovilidad en cuatro sesiones cada 72 horas). Transcurridas 3 semanas, fueron evaluados de nuevo sus niveles de IPP. Los resultados muestran que las diferencias significativas entre los sujetos con alta y baja IPP se mantienen en la sesión post-estrés (p

Cocaine addiction is a chronic disorder with high relapse rates; therefore, understanding the neuronal mechanisms underlying drug-seeking during relapse is a priority to develop targeted pharmacotherapy. The metabotropic glutamate receptor 5 (mGluR5) seems to be involved in the reinstatement induced by cocaine-associated cues. The main objective of the study was to evaluate the efficacy of MPEP, a negative allosteric modulator of mGluR5, in attenuating or potentiating the reinstatement induced by priming doses of cocaine in the CPP paradigm, ultimately to further knowledge regarding the role of the mGluR5 in relapse into cocaine abuse. OF1 mice (48 female and 48 male) were conditioned in the CPP paradigm with cocaine (20 mg/kg) and were exposed to an extinction program. We evaluated the efficacy of MPEP (30 mg/kg) in blocking the successive cocaine-priming reinstatements in the CPP when extinction of the conditioning preference was confirmed. MPEP did not block the reinstatement of priming cocaine-induced CPP, but increased the potential of cocaine for reinstating conditioning preference. The contingent administration of MPEP with cocaine increased the drug-seeking behaviour and the number of reinstatements with priming doses of cocaine. Moreover, MPEP produced cross reinstatement of cocaine-induced CPP. Rather than preventing the reinstatements of conditioned preference induced by priming doses of cocaine, MPEP increased them. These findings may help to understand the role of mGluR5 in the relapse into cocaine abuse.La adicción a la cocaína es un trastorno crónico con un alto índice de recaídas; por tanto, es prioritario entender los mecanismos neurales implicados en la búsqueda de la droga durante la recaída para desarrollar farmacoterapias eficaces. El receptor metabotrópico 5 del glutamato (mGluR5) parece estar implicado en la reinstauración inducida por las claves asociadas a la cocaína. El objetivo principal de este estudio fue profundizar en el papel del receptor mGluR5 en la recaída en el consumo de cocaína, evaluando el efecto del MPEP, un modulador alostérico negativo del mGluR5, sobre la reinstauración inducida por un priming de cocaína en el paradigma del condicionamiento de la preferencia de lugar (CPL). Ratones OF1 (48 machos y 48 hembras) fueron condicionados en el paradigma del CPL con cocaína (20 mg/kg) y expuestos a un programa de extinción. Cuando la extinción de la preferencia condicionada fue confirmada, se evaluó la eficacia del MPEP (30 mg/kg) para bloquear las sucesivas reinstauraciones mediante priming de cocaína en el CPL. La administración contingente de MPEP con la cocaína en el CPL incrementó la conducta de búsqueda de la droga y el número de reinstauraciones. Además, la administración solo de MPEP produjo reinstauración cruzada en el CPL inducido por cocaína. Por tanto, el MPEP no solo no previno, sino que incrementó las reinstauraciones de la preferencia condicionada inducida por priming de cocaína. Estos resultados pueden ayudar a entender el papel del mGluR5 en la recaída al consumo de cocaína.

Novelty seeking (NS), defined as a tendency to pursue novel and intense emotional sensations and experiences, is one of the most relevant individual factors predicting drug use among humans. High novelty seeking (HNS) individuals present an increased risk of drug use compared to low novelty seekers. The NS endophenotype may explain some of the differences observed among individuals exposed to drugs of abuse in adolescence. However, there is little research about the particular response of adolescents to drugs of abuse in function of this endophenotype, and the data that do exist are inconclusive. The present work reviews the literature regarding the influence of NS on psychostimulant reward, with particular focus on adolescent subjects. First, the different animal models of NS and the importance of this endophenotype in adolescence are discussed. Later, studies that have used the most common animal models of reward (self-administration, conditioned place preference paradigms) to evaluate how the NS trait influences the rewarding effects of psychostimulants are reviewed. Finally, possible explanations for the enhanced risk of developing substance dependence among HNS individuals are discussed. In conclusion, the studies referred to in this review show that the HNS trait is associated with: (1) increased initial sensitivity to the rewarding effects of psychostimulants, (2) a higher level of drug craving when the subject is exposed to the environmental cues associated with the drug, and (3) enhanced long-term vulnerability to relapse to drug consumption after prolonged abstinence.

Novelty-seeking in rodents, defined as enhanced specific exploration of novel situations, is considered to predict the response of animals to drugs of abuse and, thus, allow "drug-vulnerable" individuals to be identified. The main objective of this study was to assess the predictive ability of two well-known paradigms of the novelty-seeking trait - novelty-induced locomotor activity (which distinguishes High- and Low-Responder mice, depending on their motor activity) and the hole-board test (which determines High- and Low-Novelty Seeker mice depending on the number of head dips they perform) - to identify subjects that would subsequently be more sensitive to the conditioned rewarding effects of cocaine in a population of young adult (PND 56) and adolescent (PND 35) OF1 mice of both sexes. Conditioned place preference (CPP), a useful tool for evaluating the sensitivity of individuals to the incentive properties of addictive drugs, was induced with a sub-threshold dose of cocaine (1 mg/kg, i.p.). Our results showed that novelty-induced motor activity had a greater predictive capacity to identify "vulnerable-drug" individuals among young-adult mice (PND 56), while the hole-board test was more effective in adolescents (PND 35). High-NR young-adults, which presented higher motor activity in the first ten minutes of the test (novelty-reactivity), were 3.9 times more likely to develop cocaine-induced CPP than Low-NR young-adults. When total activity (1h) was evaluated (novelty-habituation), only High-R (novelty-non-habituating) young-adult male and Low-R (novelty-habituating) female mice produced a high conditioning score. However, only High-Novelty Seeker male and female adolescents and Low-Novelty Seeker female young-adult animals (according to the hole-board test), acquired cocaine-induced CPP. These findings should contribute to the development of screening methods for identifying at-risk human drug users and prevention strategies for those with specific vulnerabilities.

The influence of anxiety on the effects of acute stress for the acquisition and retention of passive avoidance conditioned task was evaluated in male and female mice. Animals were categorized as high-, medium-, and low-anxiety according to their performance in the elevated plus-maze test. Subsequently, half of the mice in each group were exposed to an acute stressor and assayed in an aversive conditioning test two days later. Exposure to restraint stress before inhibitory avoidance conditioning had a differential impact on the conditioned response of males and females according to their trait anxiety. The acute stressor significantly altered the conditioned response of mice with a high-anxiety level. The long-term effect of the stressor varied for each sex; high-anxiety stressed males showed an enhanced conditioned response with respect to their controls, whereas high-anxiety stressed females presented an impaired performance. These results lead us to believe that the characterization of individuality is an important factor in understanding the interaction between stress and memory for each sex; the trait anxiety of our animals modulated the effects of stress on the conditioned response so that males and females performed in contrasting manners to the same environmental stimuli and experimental conditions.

Cocaine addiction is a chronic disorder with high relapse rates; therefore, understanding the neuronal mechanisms underlying drug-seeking during relapse is a priority to develop targeted pharmacotherapy. The metabotropic glutamate receptor 5 (mGluR5) seems to be involved in the reinstatement induced by cocaine-associated cues. The main objective of the study was to evaluate the efficacy of MPEP, a negative allosteric modulator of mGluR5, in attenuating or potentiating the reinstatement induced by priming doses of cocaine in the CPP paradigm, ultimately to further knowledge regarding the role of the mGluR5 in relapse into cocaine abuse. OF1 mice (48 female and 48 male) were conditioned in the CPP paradigm with cocaine (20 mg/kg) and were exposed to an extinction program. We evaluated the efficacy of MPEP (30 mg/kg) in blocking the successive cocaine-priming reinstatements in the CPP when extinction of the conditioning preference was confirmed. MPEP did not block the reinstatement of priming cocaine-induced CPP, but increased the potential of cocaine for reinstating conditioning preference. The contingent administration of MPEP with cocaine increased the drug-seeking behaviour and the number of reinstatements with priming doses of cocaine. Moreover, MPEP produced cross reinstatement of cocaine-induced CPP. Rather than preventing the reinstatements of conditioned preference induced by priming doses of cocaine, MPEP increased them. These findings may help to understand the role of mGluR5 in the relapse into cocaine abuse.

Novelty-seeking in rodents, defined as enhanced specific exploration of novel situations, is considered to predict the response of animals to drugs of abuse and, thus, identify "drug-vulnerable" individuals. The main objective of this work was to determine the capacity of two animal models-the novel object recognition task and the novel environment test-for evaluating to what extent novelty-seeking can predict greater sensitivity to the rewarding properties of cocaine in young adult (PND 56) and adolescent (PND 35) OF1 mice of both sexes. Conditioned place preference, a useful tool for evaluating the sensitivity of individuals to the incentive properties of addictive drugs, was induced with a sub-threshold dose of cocaine (1 mg/kg, i.p.). Three factors that predispose individuals to addiction were considered: age, sex and novelty-seeking trait. CPP was detected only in the young adults that spent most time exploring the novel environment (High Novel Environment Seekers, High-Environment-NS). The novel environment test seemed to be more effective than the novel object recognition task in identifying young adults vulnerable to drugs; specifically, it revealed a distinction between High- and Low-Environment-NS mice that predicted greater sensitivity to the rewarding properties of cocaine among young adults but not among adolescents. Although our results reveal a higher novelty preference among young adult females than among their male counterparts in the two NS tests, both sexes showed similar susceptibility to the rewarding effects of a sub-threshold dose of cocaine in the CPP. These findings suggest that screening can identify humans at-risk of becoming drug users, and may contribute to the development of prevention strategies based on specific vulnerabilities.

This is a selective review of the literature concerning the effects of antidepressant drugs on animal memory, which was performed with the aid of the PubMed database. Monoamine oxidase inhibitors tend to either have no effect on memory or result in its improvement. Studies with cyclic antidepressants have reported no effect or, more often, memory impairments. Pre-training administration of selective serotonin reuptake inhibitors (SSRIs) has been shown to have either no effect on memory or undermine it (with some isolated exceptions, in which improvements have been recorded), while post-training administration of SSRIs has been demonstrated to improve memory or have no effect. A small group formed by the remaining antidepressants has been shown to improve memory, with the exception of trazodone, which impairs memory. These findings are discussed in the light of knowledge regarding the actions of antidepressants on several neurotransmission systems. The possibility that the effects of antidepressants on memory are the core of the therapeutic effects of these drugs is also considered.

The relation between the use of cannabis and violent behavior is controversial, partly owing to the complexity of the concept of aggression and variability among the studies performed. The primary psychoactive compound of cannabis, Δ9-tetrahydrocannabinol, acts on G-protein-coupled receptors such as the cannabinoid type 1 (CB1) receptor, the most important of the endocannabinoid system. Although historically suspected of instigating aggressive behaviors, the findings of research about cannabis use in humans are mixed. While cannabis intoxication seems to reduce the likelihood of violence, mounting evidence associates withdrawal with an increase in aggression. Acute or chronic cannabis administration in animal models correlates with decreases in aggression, a result confirmed by studies in mice lacking the CB1 receptor. In conclusion, human and animal studies have shown that cannabis use does not lead to increases in aggressive behavior, but rather the opposite. However, under certain circumstances, such as discontinuation of chronic use, aggression can be heightened.

State-dependent learning (SDL) is a phenomenon in which the retrieval of newly acquired information is possible if the subject is in the same physiological state as during the encoding phase. SDL makes it possible to separate the effects of drugs per se on learning from the effects due to changes in drug state during the task. The present work was designed to investigate whether the antidepressants amitriptyline (30 mg/kg), maprotiline (25 mg/kg), and fluoxetine (15 mg/kg) produce SDL of the inhibitory avoidance conditioning in male and female CD1 mice. In three separate experiments, independent groups were used for each pharmacological treatment and for each sex using a 2 × 2 experimental design. The results do not show SDL in any of the drugs. In the case of amitriptilyline, the data can be attributed to a memorization deficit, while the maprotiline results are interpreted as simultaneously influenced by memorization deficit and performance facilitation due to motor impairment. Fluoxetine treatment did not produce any deteriorating effect on the conditioning. Drugs had some different effects on the performance of males and females, males showing a slightly higher deterioration than females with administration of amitriptyline and maprotiline. This study shows that these antidepressants affect the acquisition/consolidation but not the retrieval process in the inhibitory avoidance learning.

The effects of chronic administration of fluoxetine (20 mg/kg/day i.p.) on a one-trial step-through inhibitory avoidance task were investigated in male and female CD1 mice. In Experiment 1, treatment was administered for 21 days before the training session, whereas in Experiment 2, other subjects were subjected to the same treatment starting 24 h after the training session. The comparison of test versus training latencies showed memory deterioration with pre-training administration of fluoxetine (Experiment 1), which affected males but not females. Sex differences in this task were also observed in Experiment 1, with females showing a better performance. Sex differences were evident in controls as well as in treated animals. The locomotor activity of the animals was also tested in Experiment 1. Due to the absence of sex differences in the drug effects on this measure, the sex differences in the effects of fluoxetine on inhibitory avoidance were hardly attributable to non specific effects on locomotor activity. The lack of effect of post-training administration of fluoxetine (Experiment 2) constitutes additional support of the idea that the observed effect on inhibitory avoidance in Experiment 1 is specifically related to learning and memory.

The effects of acute administration of amitriptyline on memory consolidation in male and female CD1 mice were investigated. Three doses of this tricyclic antidepressant (7.5, 15 and 30 mg/kg) were administered immediately after inhibitory avoidance training. Forty-five minutes after injection, subjects explored the elevated plus-maze for five minutes. Subjects were tested for avoidance twenty-four hours later. Amitriptyline impaired inhibitory avoidance consolidation at doses 7.5, 15 and 30 mg/kg in males, and at doses 7.5 and 30 mg/kg in females. In the elevated plus-maze, amitriptyline had no effect on anxiety (percentage of open arm entries) and induced a dose-dependent impairment of activity (number of closed arm entries). The observed sex differences were limited to subtle stronger effects of amitriptyline in males than in females on inhibitory avoidance. These results indicate that acute amitriptyline administration produces retrograde amnesia on inhibitory avoidance, which does not seem be mediated by anxiolytic effects.

Chronic cannabinoid consumption is an increasingly common behavior among teenagers and has been shown to cause long-lasting neurobehavioral alterations. Besides, it has been demonstrated that cocaine addiction in adulthood is highly correlated with cannabis abuse during adolescence. Cocaine consumption and subsequent abstinence from it can cause psychiatric symptoms, such as psychosis, cognitive impairment, anxiety, and depression. The aim of the present research was to study the consequences of adolescent exposure to cannabis on the psychiatric-like effects promoted by cocaine withdrawal in adult mice. We pre-treated juvenile mice with the cannabinoid CB1 receptor agonist WIN 55212-2 (WIN) and then subjected them to a chronic cocaine treatment during adulthood. Following these treatments, animals were tested under cocaine withdrawal in the following paradigms: pre-pulse inhibition, object recognition, elevated plus maze, and tail suspension. The long-term psychotic-like actions induced by WIN were not modified after cocaine cessation. Moreover, the memory impairments induced by cocaine withdrawal were not altered by previous adolescent WIN intake. However, WIN pre-treatment prevented the anxiogenic effects observed after cocaine abstinence, and led to greater depressive-like symptoms following cocaine removal in adulthood. This study is the first to show the long-lasting behavioral consequences of juvenile exposure to WIN on cocaine withdrawal in adult mice.

Exposure to drugs such as ethanol or cocaine during adolescence induces alterations in the central nervous system that are modulated by the novelty-seeking trait. Our aim was to evaluate the influence of this trait on the long-term effects of MDMA administration during adolescence on spontaneous behavior and conditioned rewarding effects in adulthood. Adolescent mice were classified as high or low novelty seekers (HNS or LNS) according to the hole-board test and received either MDMA (0, 10 or 20mg/kg PND 33-42) or saline. Three weeks later, having entered adulthood (PND>68), one set of mice performed the elevated plus maze and social interaction tests, while another set performed the conditioning place preference (CPP) test induced by cocaine-(1mg/kg) or MDMA-(1mg/kg). Only HNS mice treated with MDMA during adolescence acquired CPP in adulthood with a non-effective dose of cocaine or MDMA. Although it did not produce changes in motor activity, exposure to MDMA during adolescence was associated with more aggressive behaviors (threat and attack) and increased social contacts in HNS mice, while an anxiolytic effect was noted in LNS mice pre-treated with the highest dose of MDMA (20mg/kg). Administration of MDMA (10 or 20mg/kg) induced a decrease in DA levels in the striatum in LNS mice only and lower striatal serotonin levels in mice treated with the highest MDMA dose. Our findings show that adolescent MDMA exposure results in higher sensitivity to the conditioned reinforcing properties of MDMA and cocaine in adult HNS mice, which suggests that the relationship between exposure to MDMA in adolescence and a higher probability of substance is a feature of high novelty seekers only.

Male CB1KO mice exhibit stronger aggressive responses than wild-type mice. This study was designed to examine the role of cannabinoid CB2r in social and aggressive behavior. The social interaction test and resident–intruder paradigm were performed in mice lacking CB2r (CB2KO) and in wild-type (WT) littermates. The effects of the CB2r selective agonist JWH133 (1 and 2 mg/kg) on aggression were also evaluated in Oncins France 1 (OF1) mice. Gene expression analyses of monoamine oxidase-A (MAO-A), catechol-o-methyltransferase (COMT), 5-hydroxytryptamine transporter (5-HTT), and 5-HT1B receptor (5HT1Br) in the dorsal raphe nuclei (DR) and the amygdala (AMY) were carried out using real-time PCR. Group-housed CB2KO mice exhibited higher levels of aggression in the social interaction test and displayed more aggression than resident WT mice. Isolation increased aggressive behavior in WT mice but did not affect CB2KO animals; however, the latter mice exhibited higher levels of social interaction with their WT counterparts. MAO-A and 5-HTT gene expression was significantly higher in grouped CB2KO mice. The expression of 5HT1Br, COMT, and MAO-A in the AMY was more pronounced in CB2KO mice than in WT counterparts. Acute administration of the CB2 agonist JWH133 significantly reduced the level of aggression in aggressive isolated OF1 mice, an effect that decreased after pretreatment with the CB2 receptor antagonist AM630. Our results suggest that CB2r is implicated in social interaction and aggressive behavior and deserves further consideration as a potential new target for the management of aggression.

The effects of acute administration of fluoxetine on memory consolidation using an inhibitory avoidance task were investigated in male and female OF1 mice. Several doses of this antidepressant (5, 10, and 20 mg/kg) were intraperitoneally administered immediately after the training session. The test session was carried out four days later and response latencies were measured in both sessions. The results showed that the highest dose of fluoxetine significantly increased response latencies of inhibitory avoidance compared with the lowest dose and the control group. Sex differences in this task were observed, females showing a better performance. But the drug's effects were not sexually dimorphic: These sex differences were present in control animals, and they remained at every dose of fluoxetine. It is concluded that acute administration of fluoxetine did not impair inhibitory avoidance learning and it could be a better choice in depression and other disorders associated with memory deficits.

The antibiotic anisomycin inhibits protein synthesis, which much research has suggested is required for the formation of long-term memory. The present work studied the effects of acute subcutaneous administration of anisomycin on the consolidation of memory in an inhibitory avoidance task in CD1 mice of both sexes. The animals were separated by sex and randomly distributed into three groups: two groups were injected with 150 mg/kg anisomycin, one immediately after the training phase and the other 24 h later, while the control group received saline. The interval between training and test was four days. Anisomycin administrated immediately after training produced statistically significant impairment of memory, which was not observed when the drug was administered 24 h after training. No sex differences were observed in the effects of anisomycin. These results extend to female mice the memory impairing effects of anisomycin previously observed in males and endorse the hypothesis that the establishment of long-term memory depends on protein synthesis shortly after training.

In Experiment 1, the effect of the administration of the antidepressant amitriptyline (30 mg/kg) for 21 days on the acquisition and consolidation of the inhibitory avoidance task was studied in male and female mice. In Experiment 2, it was evaluated whether amitriptyline administered after the consolidation of this task would block the memory retrieval. Anxiety and spontaneous activity in the elevated plus maze were also assessed. When amitriptyline was given before the training phase of inhibitory avoidance it blocked learning in males and there was a tendency in the same direction in females. However, the drug administered between training and test phases did not affect conditioning. These effects of amitriptyline seem to be independent of its actions on anxiety and locomotor activity. It may be that the effects observed are related to the therapeutic effects of antidepressants.

The acute effects of maprotiline (2.5, 5, 10, 15, 20 or 25 mg/kg) on learning, anxiety, activity and analgesia in male and female mice were evaluated. In addition to inhibitory avoidance learning, anxiety and locomotor activity were measured in the same animals using an elevated plus-maze. A study of the acute effects of maprotiline (15, 20 or 25 mg/kg) on analgesia was carried out in naive animals of both sexes. Maprotiline impaired inhibitory avoidance at doses of 15, 20 or 25 mg/kg. The highest dose produced an anxiolytic effect in females, and the doses of 20 and 25 mg/kg reduced locomotor activity. Analgesia was observed with the highest dose. The impairment of inhibitory avoidance by maprotiline would seem to be independent of the drug's influence on anxiety, is not shadowed by an instrumental performance deficit and, at least in the case of the highest dose, could be influenced by the drug's effects on analgesia. It is hypothesized that acquisition is the memory process principally affected by maprotiline, and in particular stimuli processing. The lack of sex differences in the effects of maprotiline on inhibitory avoidance supports the generalization of findings previously obtained only in males.

The purpose of the present work was to study the effects of amitriptyline on animal cognition in relation to some characteristics of its therapeutic effects. The modulation of acute and chronic effects of amitriptyline on inhibitory avoidance in male and female mice by piracetam was investigated. In Experiment 1, mice were subjected to the training phase of inhibitory avoidance conditioning 60 min after acute piracetam (100 mg/kg) or physiological saline administration. Immediately after the behavioural task, they received a single injection of the tricyclic antidepressant amitriptyline (30 mg/kg) or physiological saline. Twenty-four hours later, subjects were tested for avoidance. In Experiment 2, the same doses of amitriptyline and piracetam were chronically administered. Mice were subjected to the training phase of inhibitory avoidance on the 22nd day, and to the test phase 24 h later. Forty-five minutes after test, subjects explored the elevated plus-maze for 5 min in order to assess whether the effects of amitriptyline on avoidance performance may reflect general behavioural changes. Results obtained were that: (a) acute and chronic amitriptyline impaired inhibitory avoidance of male and female mice, (b) piracetam counteracted the effect of acutely administered amitriptyline on inhibitory avoidance, and (c) piracetam counteracted the effects of chronically administered amitriptyline in males but not females in the same learning task. These effects do not seem to be mediated by non-specific drug effects on spontaneous motor activity or anxiety.

with electrochemical detection. All the data were compared to their respective controls using Student’s t-test. Results: Restraint stress significantly increased 5-HT turnover in both mice strains. Compared to saline-treated mice, the stressinduced increase of 5-HT turnover was reduced in the C57BL/6J and the BALB/c mice, respectively, by 67±17% and 76±10% after treatment with a 3mg/kg dose of RO 60–0175. Neither the GABA-B receptor antagonist phaclofen nor the specific genetic ablation of either GABA-B1a or GABA-B1b subunits altered the inhibitory effect of RO 60–0175. Interestingly, however, 5-HT turnover was markedly decreased in GABA-B1a knock-out mice in both stress and basal conditions (GABA-B1a−/−= 0.60±0.04, WT= 0.80±0.04, means±S.E.M., n = 6−9; p< 0.01). In contrast to pharmacological blockade of GABA-B receptor, the GABA-A receptor antagonist bicuculline significantly reduced the 5-HT2C receptor-mediated inhibition of 5-HT turnover. A significant effect of 5-HT2C receptor activation persisted, however, in mutant mice deficient in the alpha3 subunit of GABA-A receptors. Conclusion: It can be inferred that non alpha3 subunitcontaining GABA-A receptors, but not GABA-B receptors, mediate the 5-HT2C-induced inhibition of stress-induced increase of hippocampal 5-HT turnover in mice. Since glutamatergic terminals mainly express the GABA-B1a subunit [3], the reduction in 5-HT turnover observed in GABA-B1a−/− mice might be explained by a stronger excitatory glutamatergic input onto GABAergic interneurons inhibiting 5-HT neurons in raphe nuclei, resulting from a lack of negative feedback on glutamatergic terminals via GABA-B heteroreceptors.

Gender differences in the disruptive effects of haloperidol on some reinforced behaviors have been observed in different species. However, the inhibitory action of haloperidol on the acquisition and performance of escape-avoidance behavior has only been investigated in male subjects. The present experiment was designed to investigate possible gender differences in the effects of haloperidol on the initial phase of an escape-avoidance learning task. Male and female mice of the OF1 strain were given a single training session in a shuttle-box. Thirty minutes prior to the behavioral test, mice were injected IP with haloperidol (0.25 mg/kg) or physiological saline (10 ml/kg). Latencies of escape and avoidance responses and the number of nonresponses, escapes, avoidances, pseudoavoidances, crossings during the adaptation period, and crossings during intertrial intervals (ITIs) were evaluated. The disruptive action of haloperidol on the escape-avoidance behavior of the mice was greater in males than in females. The number of nonresponses were higher and the number of escapes lower in treated males than in their female counterparts. These gender differences were not found in control subjects. Activity measures of spontaneous motor behavior (crossings in the adaptation period and during ITIs) did not present gender differences either. Several possible mechanisms responsible for this greater susceptibility of males to the inhibitory effects of haloperidol on escape-avoidance learning are discussed, especially the modulating role of female hormones on dopaminergic activity.

Los trastornos de ansiedad son, en la actualidad, enfermedades psiquiátricas muy frecuentes e incapacitantes. Las mujeres en edad reproductiva son más vulnerables a desarrollar trastornos de ansiedad, aproximadamente entre 2 a 3 veces más que los hombres. Ser hombre o mujer no sólo puede influir en la prevalencia de los trastornos mentales, sino también en la manifestación y expresión de los síntomas, la voluntad para solicitar asistencia médica o psicológica, el curso de la enfermedad, incluso en la respuesta al tratamiento. Cada vez hay pruebas más sólidas de que existen diferencias entre ambos sexos respecto a la anatomía cerebral, la neuroquímica y los patrones de activación y respuesta a los estímulos ambientales; diferencias que pueden influir en la etiología y el curso de los trastornos psiquiátricos. Sin embargo, poco se conoce sobre los factores de riesgo que inducen a las mujeres a desarrollar ciertas psicopatologías. Por ello, en este trabajo pretendemos presentar una breve revisión sobre los aspectos psicobiológicos que pueden contribuir a las diferencias de sexo en los trastornos de ansiedad.