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R M Escorihuela

Publications and source records attributed to R M Escorihuela.

14 recordsLinked to original sources

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

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

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

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

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

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

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

Effects of different handling-stimulation procedures and benzodiazepines on two-way active avoidance acquisition in rats.

The acquisition of two-way active (shuttlebox) avoidance involves a conflict situation which can be used as an animal model of anxiety, since it is sensitive to manipulations of the animal's emotivity/reactivity. The results from the present study (experiment 1) add relevant support to that proposal, since diazepam (2 and 4 mg/kg) and the triazolobenzodiazepine alprazolam (1, 1.25 and 1.5 mg/kg) significantly improved avoidance performance in shuttlebox acquisition in rats in agreement with previous data. In another study (experiment 2), a mild stressful (10-day) handling procedure (i.e. handling which tends to increase the emotional reactivity of the animals, as showed in experiment 3) was found to affect such behaviour in an opposite direction to that of the two benzodiazepines. Conversely, when an habituating handling procedure (i.e. handling which leads to less reactive animals; experiment 3) was used, the acquisition of shuttlebox avoidance was improved (experiment 4). The results are discussed in relation with previous data showing that the particular parameters used in the exposure to stressful stimuli may lead to either sensitization or habituation of anxious responses.

Alprazolam

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

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

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

Sodium valproate reduces immobility in the behavioral 'despair' test in rats.

The present study was conducted to investigate whether sodium valproate could affect immobility in the 'behavioral despair' test in rats. Acute (one injection), subacute (three injections) and chronic treatment with sodium valproate reduced the immobility time in this test, whereas a stimulation of motor activity in the open-field test was not observed with the same drug treatments. The anti-immobility activity of valproate was partially counteracted by the administration of bicuculline (2 mg/kg) or picrotoxin (1.4 mg/kg) before the immobility test. The data agree with previous findings from several animal models of depression of an antidepressant-like activity of GABA mimetics or agents which stimulate GABAergic function.

Animals

Imipramine and desipramine decrease the GABA-stimulated chloride uptake, and antigabaergic agents enhance their action in the forced swimming test in rats.

The present study reports that long-term (18 days) administration of imipramine (IMI, 20 mg/kg) or desipramine (DMI, 15 mg/kg) produced a significant decrease in the GABA-stimulated 36Cl- uptake into membrane vesicles from the cerebral cortex of rats (experiment 1). Experiments 2A, B show that anti-immobility effects of DMI and IMI (subacute treatment) in the forced swimming test are enhanced when a single subconvulsant injection of picrotoxin or pentylenetetrazol is administered to the animals concurrently to the last antidepressant injection. These results are discussed in relation with a current GABAergic hypothesis of depression and antidepressant drug action.

Animals