Biomedical subjects

A Tobeña

Publications and source records attributed to A Tobeña.

At least 37 records · Page 2Linked to original sources

PubMed1995

Behavior of the Roman/Verh high- and low-avoidance rat lines in anxiety tests: relationship with defecation and self-grooming.

The Swiss sublines of Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats have been selected and bred for rapid (RHA/Verh) vs. extremely poor (RLA/Verh) acquisition of two-way active avoidance. Behavioral and physiological measures of emotionality, or reactivity to stress, appear to be among the most prominent characteristics differentiating both rat lines. The present study shows that RLA/Verh rats are more sensitive, as compared to their RHA/Verh counterparts, to the conflict involved in the shock-induced suppression of drinking paradigm, as well as in a hyponeophagia test. RLA/Verh rats also showed higher defecation values which were significantly correlated with the main hyponeophagia test variables. Likewise, self-grooming was more frequent in RLA/Verh rats than in their RHA/Verh counterparts and showed significant correlations with conflict-related behaviors (i.e., latency to start eating and time spent eating) from the hyponeophagia test. These results give additional support to the contention that RLA/Verh rats present higher anxiety (emotionality) than their RHA/Verh counterparts.

Animals↗

PubMed1995

Effects of training, early handling, and perinatal flumazenil on shuttle box acquisition in Roman low-avoidance rats: toward overcoming a genetic deficit.

The present series of studies investigated the effects of intensive training, postnatal handling-stimulation and/or perinatal flumazenil (Ro 15-1788, benzodiazepine receptor antagonist) on the acquisition of two-way active avoidance by Roman low-avoidance (RLA/Verh) rats. This rat line has been selectively bred for poor avoidance in the shuttle box, while their Roman high-avoidance counterparts (RHA/Verh) have been selectively bred for their extremely good performance in that task. In the first experiment, RLA/Verh rats submitted to a long and intensive training procedure (unlike those submitted to short training) were able to achieve a performance of 56% of avoidances per session. In the second experiment both postnatal handling and perinatal flumazenil treatments increased avoidance responding in another group of RLA/Verh rats tested at the age of 18 months. Finally, in the last experiment, the performance of a third stock of RLA/Verh rats of the same age which had received perinatal flumazenil did not differ, on the later phases of training, from that shown by RHA/Verh animals. The results are discussed in terms of the "warm up" phenomena which seems to be highly involved in the selection of RLA/Verh rats, as well as on the possibility that central benzodiazepine receptors could play a role in the genetic deficit shown by RLA/Verh rats, which apparently confers a greater emotivity.

Animals↗

PubMed1994

Environmental enrichment reverses the detrimental action of early inconsistent stimulation and increases the beneficial effects of postnatal handling on shuttlebox learning in adult rats.

Certain types of environmental stimulation administered during critical periods of neural development can enduringly modify adult behavior. The present experiments show that postnatal handling of Sprague-Dawley rats (administered from postnatal days 1 to 22) and/or living in an enriched environment (EE; from weaning until the age of 100 days) clearly improved the ability to learn a two-way active avoidance task in adulthood. In addition the results demonstrated that postnatal inconsistent stimulation (from postnatal days 1 to 22) impaired avoidance acquisition in the same task. This detrimental effect of inconsistent stimulation was reversed by EE. Our findings provide evidence that different types of early experience can influence learning abilities in distinct directions and with different strengths.

Aging↗

PubMed1994

Evaluating activity and emotional reactivity in a hexagonal tunnel maze: correlational and factorial analysis from a study with the Roman/Verh rat lines.

Two hundred forty 30-day-old Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats (divided equally by line and gender) which had received several peri- and/or postnatal treatments, forming two factorial [line x sex x treatment(s)] experimental designs, were tested in a hexagonal tunnel maze including a brightly illuminated central arena. The present study reports the results of correlational and factorial (principal-components) analyses performed on the data from those two experimental constituencies. The purpose of the study was to evaluate the validity of the hexagonal tunnel maze for testing emotionality, and therefore, the following measures were included in the analysis: entries into the central illuminated arena, total activity during testing, defecation during testing, and defecation during handling and weighing after testing. An overall pattern of negative correlations (or opposite loadings in the principal-components analyses) between defecation (especially during maze testing) and entries into the illuminated center and activity was found, thus giving support to the validity of entries into the illuminated center as being indicative of emotional reactivity.

Animals↗

PubMed1994

Differential interactions between ethanol and Ro 15-4513 on two anxiety tests in rats.

The effects of low (2 g/kg) and high (4 g/kg) doses of ethanol and their interaction with the imidazobenzodiazepine Ro 15-4513 (a partial inverse agonist of the benzodiazepine receptor) were studied in two different models of anxiety in rats: the "elevated plus-maze" test and the early acquisition of two-way (shuttlebox) avoidance. In the elevated plus-maze, ethanol (2 g/kg) increased the percentage of entries into the open arms (%EOA) and both ethanol doses increased the percentage of time spent into the open arms (%TOA), thus indicating an anxiolytic action which was reversed by Ro 15-4513 (5 mg/kg). By contrast, Ro 15-4513 did not counteract the anxiolytic effect of the low dose of ethanol in the acquisition of shuttlebox avoidance. Thus, the treatment with 2 g/kg of ethanol (plus either vehicle or Ro 15-4513) significantly increased the total number of avoidances. Conversely, animals treated with 4 g/kg of ethanol showed impaired shuttlebox avoidance acquisition, and this effect was completely reversed by Ro 15-4513. Ro 15-4513 was without effect on its own in any of the anxiety-related parameters (i.e., %EOA, %TOA, and avoidance acquisition). The results indicate a different pattern of ethanol effects and Ethanol x Ro 15-4513 interactions depending upon the task used.

Animals↗

PubMed1994

Struggling and flumazenil effects in the swimming test are related to the level of anxiety in mice.

The possible involvement of anxiety and learning/memory processes in escape-directed (struggling) behavior in a two-trial swimming test was investigated in mice, as well as the differential effects that low doses of flumazenil (a benzodiazepine receptor antagonist) could display depending on the animals' anxiety levels. Mice showing less anxiety in the plus-maze test exhibited less struggling behavior in the first swimming trial than the more anxious animals, suggesting a relationship between anxiety and struggling behavior in the swimming test. Flumazenil (5 mg/kg) given before the first swimming trial displayed differential effects depending upon the animals' anxiety levels. Thus, it increased struggling behavior in the first swimming trial in 'low-anxiety' mice whereas the opposite tendency was observed in 'high-anxiety' animals. Struggling decreased in the second swimming trial in all the animals, giving support to the involvement of learning/memory processes in the two-trial swimming test. That reduction in escape-directed behavior was greater in animals treated with flumazenil before the first swimming session, thus indicating a slight enhancement of retention.

Animals↗

PubMed1993

Postnatal handling, perinatal flumazenil, and adult behavior of the Roman rat lines.

The effect of infantile handling stimulation and/or perinatal flumazenil (Ro 15-1788; a benzodiazepine receptor antagonist; 3.7 mg/kg/day) administration on exploratory and emotional-related behavior was investigated using adult females from the Roman high- and low-avoidance (RHA/Verh and RLA/Verh) lines. When rats (6 months old) were exposed to a hexagonal tunnel maze including an illuminated central arena, it was found that RHA/Verh rats were more active, explored more maze area, showed more outward preference, and more frequently entered the illuminated center than RLA/Verh rats. In addition, postnatal stimulation decreased emotional-related behavior in both lines of rats, as expressed by increased entry into, and time spent in, the central arena. Perinatal flumazenil treatment decreased entry into the maze central arena in both rat lines but this effect was counteracted by postnatal (handling) stimulation. Thus, the present study extends to adult RHA/Verh and RLA/Verh rats the positive long-lasting effects of postnatal handling and shows postnatal handling x flumazenil interactions in some behavioral parameters related to the pattern of exploration and exploratory efficiency.

Animals↗

PubMed1993

Limits of habituation and extinction: implications for relapse prevention programs in addictions.

Problems in the application of exposure techniques to the management of long term dishabituation in addicts are discussed in the light of human and animal evidence. Extinction and habituation of responses to drug cues or drug aftereffects are unstable and strongly dependent on context, thus limiting the effectiveness of cue exposure treatments in the prevention of relapse. Several strategies are suggested to improve the stability of extinction and habituation in order to enduringly prevent relapse in addictions. (i) Warning patients about the episodic resurgence of unexpected urges or cravings precipitated by conditioned contexts and exposing them to such contexts. (ii) To obtain a maximum protection against relapse, extinction should 'recreate' all the original learning contexts (i.e. all possible drug cues). (iii) The behavioral chains involved in self administering drugs ought to be incorporated into cue exposure treatments (without permitting consummatory responses) in order to decrease their signal value as cues for drugs.

Animals↗

PubMed1992

Early stimulation effects on novelty-induced behavior in two psychogenetically-selected rat lines with divergent emotionality profiles.

The present study shows that postnatal handling (H: consisting of removing the pups from the nest twice daily and placing them individually in plastic cages lined with paper towel for a period of 10 min, between postnatal days 1 and 21) and/or environmental enrichment (E: for a period of 6 months) of Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats induced long-lasting decreases in emotional reactivity (i.e. reduced defecations in the open field, OF, and hole-board, HB, tests) as well as increases in exploratory behavior (i.e. head-dipping) in a manner dependent upon the rat line (there were 'line x H' and 'line x E' interactions). It is reported for the first time that RHA/Verh rats show more head-dipping behavior than RLA/Verh rats, and that the environmental treatments can increase head-dipping of RLA/Verh animals to the level shown by RHA/Verh rats.

Animals↗

PubMed1992

Differential effects of early stimulation and/or perinatal flumazenil treatment in young Roman low- and high-avoidance rats.

The effect of infantile handling-stimulation and/or perinatal flumazenil (3.7 mg/kg/day) administration on exploratory and emotional-related behavior was investigated using Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats. Postnatal handling increased exploration in 30-day-old rats of both psychogenetically selected lines when they were exposed to a hexagonal tunnel maze including an illuminated central arena. Likewise, postnatal stimulation decreased emotional reactivity in both lines of rats, as expressed by increased entry into the central arena, decreased defecation and vocalization frequency, but these effects were more pronounced in the RLA/Verh line. There were interactions between perinatal flumazenil treatment and rat line, indicating that flumazenil enhanced entry into the maze central arena in handled-RLA/Verh rats, whereas a tendency toward the opposite effect was observed in drug-treated and handled-RHA/Verh animals. Thus, the present study emphasizes that the effects of environmental manipulations are partly dependent upon genetic factors, and that pharmacological effects also depend on both genetic and environmentally-induced predisposition.

Animals↗

PubMed1992

Infantile stimulation and the role of the benzodiazepine receptor system in adult acquisition of two-way avoidance behavior.

The present study shows that postnatal "consistent" handling (CH) of rats had long-lasting improving effects on coping with an stressful task (i.e. two-way active avoidance), and that such effects were partially prevented by acute Ro 15-1788 (antagonist of benzodiazepine receptor-BZR; 5 mg/kg) administration. Long-lasting detrimental effects in the same task were also observed in rats which received postnatal "inconsistent" handling (INCH), effects that were slightly increased by acute Ro 15-1788 treatment. Finally, Ro 15-1788 tended to increase avoidance acquisition in non-handled (NH) animals. The observed effects of Ro 15-1788 could be partially attributed to a differential modulation of the process of avoidance acquisition depending on postnatal treatments producing different levels of emotionality.

Adaptation, Psychological↗

PubMed1991

Stress and putative endogenous ligands for benzodiazepine receptors: the importance of characteristics of the aversive situation and of differential emotionality in experimental animals.

The relationships between anxiety/stress, possible endogenous ligands for benzodiazepine receptors and the behavioral modification by drugs are discussed in this short review, including the specific characteristics of elements involved in those interactions, e.g. ones concerning the aversiveness of the stressful situation and the nature of the organism under investigation. These are important factors when considering aversive tasks, insofar as they may involve stressful conditions which differ in intensity and in the degree of control afforded the subject. These characteristics may well lead to differing functional effects on GABA-gated chloride channels or, in other words, to an incongruous balance between endogenous benzodiazepine receptor agonist and inverse agonist activity. This is not surprising, as it is well known that different forms of stressors often actually produce divergent behavioral, physiological and biochemical effects. This review also illustrates the necessity of taking into account the variable effects of stressors and/or drugs on animals differing in reactivity or emotionality, even in the case of 'non-selected' stocks. The implication is made that, by genetic and/or environmental manipulation of the emotional state of the animals used, it will be possible to obtain more clearly definable results in neuropharmacological and psychopharmacological studies.

Animals↗

PubMed1991

Beneficial effects of infantile stimulation on coping (avoidance) behavior in rats are prevented by perinatal blockade of benzodiazepine receptors with Ro 15-1788.

The present study shows that postnatal 'consistent' handling (CH; which consisted of removing the pups from the nest and placing them individually in plastic cages lined with paper towel for a period of 15 min daily between 1 and 22 postnatal days) of rats had long-lasting improving effects on coping with a stressful task (i.e. enhancement on the early acquisition of two-way active avoidance), but such effects were completely prevented when CH treatment was combined with chronic perinatal Ro 15-1788 (7 mg/kg/day, between prenatal day 19 and postnatal day 22) administration (i.e. blockade of benzodiazepine receptor (BZR)). A long-lasting decremental effect was also observed in the same task in rats which received postnatal 'inconsistent' handling (INCH; in which stimulation of pups was changed every day between 1 and 22 postnatal days), without being affected by the concomitant perinatal Ro 15-1788 treatment. These results suggest that intact ontogeny of BZRs is necessary to obtain the enduring positive effects of CH on emotional behavior (i.e. early acquisition of two-way active avoidance).

Adaptation, Psychological↗

PubMed1991

Infantile (handling) stimulation and behavior in young Roman high- and low-avoidance rats.

The effect of infantile handling stimulation on exploratory and emotional behavior of Roman high- and low-avoidance (RHA/Verh and RLA/Verh) weanling rats was investigated. Postnatally handled and nonhandled, 4-week-old males and females from both psychogenetically selected lines were exposed to a hexagonal tunnel maze, including an illuminated central arena. Postnatal handling increased exploratory behavior and decreased emotional reactivity as expressed by increased entries into the central arena and a reduction in defecations in both lines of rats. These effects were more pronounced in the RLA/Verh rats. In agreement with earlier studies using nonselected adult rats, the females of both lines (especially those from the RHA/Verh line) were more sensitive than males to the positive influences of early stimulation.

Animals↗

PubMed1991

The early acquisition of two-way (shuttle-box) avoidance as an anxiety-mediated behavior: psychopharmacological validation.

Several lines of evidence have established that performance during the initial steps of acquisition on a shuttle-box avoidance task is an anxiety-mediated behavior (i.e., the differences between strains selectivity bred for emotionality; the effects of postnatal handling; the course of the corticosterone response and behavioral measures of fear during acquisition). The present study was carried out to add pharmacological evidence to that view by testing the action of anxiogenic and anxiolytic drugs. Single 40-trial sessions with mild shocks (0.4 mA-0.6 mA) were used. In the first experiments the action of sodium pentobarbital (1.25, 2.5 and 5 mg/kg) and three benzodiazepines (diazepam, 2 and 4 mg/kg; alprazolam, 1, 1.25 and 1.5 mg/kg and adinazolam, 1, 2, 4 and 6 mg/kg) were tested. The last two experiments tested a possible proanxiety action of Ro 15-4513 (2, 5 and 10 mg/kg) and FG 7142 (5, 10 and 15 mg/kg), two partial inverse agonists of benzodiazepine receptors, which previous data had suggested to be anxiogenic. The results showed that the measure of acquisition of a two-way active avoidance is a sensitive mean for detecting either anxiolytic or anxiogenic effects of drugs, independently of their effects on locomotor activity, thus suggesting that such test could be a valid model of anxiety in animals.

Animals↗

PubMed1990

Infantile stimulation and perinatal administration of Ro 15-1788: additive anxiety-reducing effects in rats.

Both postnatal handling of rat pups and perinatal treatment with Ro 15-1788 have been reported to reduce the emotional reactivity of the rats in adulthood, as measured by open field behavior, by the corticosterone response to stress, and by labyrinth and novelty-induced behaviors. We now report results obtained with a well-validated animal model of anxiety (i.e. the elevated plus-maze) that support and extend these previous findings. The results show the clearest reduction of anxiety-related behavior when postnatal handling and perinatal Ro 15-1788 administration were simultaneous.

Animals↗

PubMed1990

Picrotoxin changes the effects of imipramine and desipramine in rats in the forced swimming test.

The aim was to find whether the chloride channel blocker, picrotoxin, at subconvulsant doses could affect the activity of imipramine or desipramine in the 'forced swimming' test with rats. It was found that picrotoxin enhanced the anti-immobility effects of imipramine and desipramine whereas open field activity remained unaffected or was even decreased by the same treatments. The results seem consistent with recent reports showing direct interactions between several antidepressant drugs and the GABAA receptor/benzodiazepine receptor/chloride ionophore complex (GABAA/benzodiazepine/Cl complex). The results also conform with the hypothesis that a reduction in the functionality of this complex could be related to the clinical effects of antidepressant drugs.

Animals↗

PubMed1990

Handling-habituation prevents the effects of diazepam and alprazolam on brain serotonin levels in rats.

In two different experiments, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in rats, using HPLC with electrochemical detection, in 3 brain regions (hippocampus, cerebral cortex and hypothalamus) after acute i.p. treatment with diazepam (4 mg/kg), alprazolam (1.25 mg/kg) or vehicle. In the first experiment, rats received the acute treatment 30 min before they were sacrificed. In the second, the animals were previously habituated to handling (involving the maneuvers of injecting and sacrificing at the guillotine) daily for 15 days, before the acute administration of the drugs. Results of the acute treatment alone showed a significant increase in 5-HT levels in hippocampus and cerebral cortex, and a decrease in hypothalamus, but not differences in 5-HIAA levels, for the diazepam- and alprazolam-treated groups. After handling-habituation, no effect in the monoamine or metabolite levels appeared when the rats were treated with diazepam or alprazolam. The results are discussed in relation to the emotional changes induced by the handling procedure, and for possible connections between the mechanisms of action of handling-habituation and benzodiazepine treatments at CNS level.

Alprazolam↗