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Biomedical subjects

R M Escorihuela

Publications and source records attributed to R M Escorihuela.

At least 19 recordsLinked to original sources
PubMed2002

Enduring effects of environmental enrichment on novelty seeking, saccharin and ethanol intake in two rat lines (RHA/Verh and RLA/Verh) differing in incentive-seeking behavior.

The Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rat lines represent, respectively, low emotional/anxious and high novelty seeker vs. high emotional/anxious and low novelty seeker profiles. In the present study, RLA/Verh and RHA/Verh rats, either reared in pairs from weaning (untreated) or reared in groups of 8-10 in an enriched environment until the age of 7 months, were tested for exploratory and novelty-seeking behavior in the hole board (including novel objects under the holes), as well as for their preference for saccharin-water and ethanol-water in a two-bottle free-choice paradigm. Testing started when rats were 20 months old in order to study the long-lasting effects of differential rearing. RHA/Verh rats explored more and showed greater preference for (and intake of) saccharin as well as for ethanol than RLA/Verh rats, thus confirming their validity as a rat model for sensation/reward seeking. Environmental enrichment (EE) increased head-dipping behavior (i.e., novelty seeking) in both rat lines, without affecting locomotor activity. EE treatment increased the preference for, and volume intake of, saccharin (especially at the higher concentrations tested) in the relatively low saccharin-preferring RLA/Verh rats, and also enhanced ethanol consumption in both rat lines. Thus, the results demonstrate consistent and enduring effects of EE on incentive-seeking behavior and further the analysis of how individual differential predispositions for the need of novelty and contact with (or consumption of) rewarding substances arise through either biological (genetic) or early environmental factors, or both.

Alcohol Drinking↗
PubMed2001

Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor.

Caffeine is believed to act by blocking adenosine A(1) and A(2A) receptors (A(1)R, A(2A)R), indicating that some A(1) receptors are tonically activated. We generated mice with a targeted disruption of the second coding exon of the A(1)R (A(1)R(-/-)). These animals bred and gained weight normally and had a normal heart rate, blood pressure, and body temperature. In most behavioral tests they were similar to A(1)R(+/+) mice, but A(1)R(-/-) mice showed signs of increased anxiety. Electrophysiological recordings from hippocampal slices revealed that both adenosine-mediated inhibition and theophylline-mediated augmentation of excitatory glutamatergic neurotransmission were abolished in A(1)R(-/-) mice. In A(1)R(+/-) mice the potency of adenosine was halved, as was the number of A(1)R. In A(1)R(-/-) mice, the analgesic effect of intrathecal adenosine was lost, and thermal hyperalgesia was observed, but the analgesic effect of morphine was intact. The decrease in neuronal activity upon hypoxia was reduced both in hippocampal slices and in brainstem, and functional recovery after hypoxia was attenuated. Thus A(1)Rs do not play an essential role during development, and although they significantly influence synaptic activity, they play a nonessential role in normal physiology. However, under pathophysiological conditions, including noxious stimulation and oxygen deficiency, they are important.

Adenosine↗
PubMed2001

Transmembrane signaling through phospholipase C in cortical and hippocampal membranes of psychogenetically selected rat lines.

RATIONALE: One of the major pathways for neurotransmitter signaling involves phosphoinositide-specific and G-protein-dependent phospholipase C-beta (PLC-beta), which stimulates the formation of inositol 1,4,5-trisphosphate and diacylglycerol. Serotonergic and muscarinic-cholinergic signals in the brain are largely mediated through the hydrolysis of phosphoinositides by PLC. OBJECTIVES: The aim of the experiments reported here was to explore the potential differences in neurotransmitter receptor coupling to PLC in Roman high-avoidance (RHA)/Verh and Roman low-avoidance (RLA)/Verh rats, by examining the changes in agonist (carbachol, 5-methyltryptamine)-stimulated phosphoinositide hydrolysis in hippocampal and cortical membranes derived from the two rat lines. METHODS: To investigate changes in receptor and G-protein coupling to PLC in the brains of these two psychogenetically selected rat lines, which differ in their emotional profiles/learning abilities, we examined GTPgammaS-, agonist (carbachol, 5-methyltryptamine)-, and calcium-stimulated phosphoinositide hydrolysis in cortical and hippocampal membranes of RHA/Verh and RLA/Verh rats. RESULTS: The results indicated that calcium-induced increase in PLC activity was larger in the cortex and hippocampus of RHA/Ver rats, as compared to their RLA/Verh counterparts. Conversely, GTPgammaS- and agonist-induced PLC activity was less pronounced in the hippocampus of RHA/Verh with respect to RLA/Verh rats. Western blot analysis showed no significant differences in the relative values of the G-proteins alphaq/11 and betagamma subunits between both groups of rats in any brain region. However, the levels of PLC-beta1, PLC-beta3, and PLC-beta4 were significantly lower in the hippocampus of RHA/Verh than in RLA/Verh rats. CONCLUSIONS: It is concluded that the hippocampus of RHA/Verh rats has severe deficiencies in PLC activity stimulated by guanine nucleotides and agonists, which are specifically related to a lower level of expression of the PLC-beta type isozymes, a fact that may account for the differential behavioral phenotype observed in these psychogenetically selected rat lines.

Animals↗
PubMed2000

Differential effects of cohort removal stress on the acoustic startle response of the Roman/Verh rat strains.

Male and female rats of the inbred Roman/Verh strains, which have been psychogenetically selected and bred for good (RHA-I/Verh) and extremely poor (RLA-I/Verh) two-way avoidance acquisition, were evaluated in an acoustic startle response test. One half of the rats of each strain and sex were previously subjected to 30 min of isolation by removal of their cage partners ("cohort removal"). During the testing session each animal received 40 acoustic stimuli at interstimulus intervals of 30 seconds. The hyperemotional RLA-I/Verh rats (especially the males) showed stronger acoustic startle responses than did their RHA-I/Verh counterparts. Startle amplitudes of the RLA-I/Verh males were further enhanced by the stress of 30 min isolation, whereas cohort removal did not significantly affect startle response amplitudes in RHA-I/Verh rats of either sex or in females of the RLA-I/Verh strain.

Acoustic Stimulation↗
PubMed1999

Inbred Roman high- and low-avoidance rats: differences in anxiety, novelty-seeking, and shuttlebox behaviors.

In the present study, male inbred animals (from the 10th generation of an inbreeding program that has been carried out in parallel to that of the outbred Roman high- and low-avoidance rat lines), were compared for emotionality in different testing situations, exploratory behavior in the holeboard and two-way, active-avoidance acquisition. Compared to the inbred Roman high-avoidance (RHA-I/Verh) rats, inbred Roman low-avoidance (RLA-I-Verh) rats showed higher emotionality in the open field (reduced distance travelled and number of rearings, and increased self-grooming behavior), in the elevated plus-maze test (increased number of total and open-arm entries, reduced distance travelled in the open arms, and increased self-grooming behavior), and during the habituation period in the shuttle box (decreased number of crossings, increased self-grooming behavior and defecations). Results from the hyponeophagia test were not conclusive, probably due to the test-dependent hyperactivity shown by RHA-I/Verh rats. In the holeboard apparatus, RHA-I/Verh rats explored more than RLA-I/Verh rats, especially when novel objects were located beneath the holes. Finally, RHA-I/Verh animals rapidly acquired active, two-way (shuttlebox) avoidance, whereas RLA-I/Verh animals required four 50-trial sessions to achieve an assymptotic level of 30-40% avoidance. Thus, the behavioral patterns of the Roman inbred strains were very similar to those previously reported for the RHA/Verh outbred lines. Differences in locomotor activity, exploratory, and self-grooming behavior were actually greater between the inbred strains than between the outbred lines. Differences in defecation, however, although still significant, were not so pronounced as those noted previously at this laboratory with the outbred lines.

Animals↗
PubMed1998

Pharmacological properties of the GABA(A) receptor complex from brain regions of (hypoemotional) Roman high- and (hyperemotional) low-avoidance rats.

The pharmacological properties of benzodiazepine binding sites of the gamma-aminobutyric acid (GABA)A receptor complex from cortical, hippocampal and cerebellar membranes of Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLH/Verh) rats were investigated. No major differences between the two lines were found in the binding parameters of [3H]flunitrazepam (a non-selective agonist). [3 H]zolpidem (a Type I selective agonist) or [3 H]ethyl 8-azido-6-dihydro-5-methyl-6-oxo-4H-imidazol[1,5-a]-[1,4]benzodiazepine- 3-carboxylate (Ro15-4513) (a partial inverse agonist). Neither the Kd values nor the Bmax for these ligands differed between RHA/Verh and RLA/Verh rats in any of the brain regions studied. As a result, the proportion of Type I binding sites in cortical and hippocampal membranes of RHA/Verh and RLA/Verh rats or the 'diazepam-sensitive' and the 'diazepam-insensitive' binding sites in cerebellar membranes, calculated from the [3H]flunitrazepam and [3H]zolpidem maximal binding sites or from [3H]Ro15-4513 binding (in the absence or in presence of diazepam), respectively, was also similar. Furthermore, there were no differences between the two rat lines in the allosteric interactions between GABA and the benzodiazepine binding sites (labeled with [3H]flunitrazepam) in all three areas tested or the Type I binding sites (labeled with [3H]zolpidem) in the hippocampus. In contrast, RLA/Verh rats showed a significant reduction in the allosteric interactions between GABA and [3H]zolpidem binding sites in the cortex. As a whole, these results indicate the absence of generalized between-line differences in the GABA(A) receptor complex showing, at the same time, the existence of some specific differences in allosterism within the GABA(A) complex. These differences may contribute to the divergent emotional responses which characterize the RHA/Verh and RLA/Verh rat lines.

Animals↗
PubMed1998

Impaired short- and long-term memory in Ts65Dn mice, a model for Down syndrome.

Ts65Dn (TS), control littermates (CO) and Swiss (SW) male mice were tested in the elevated plus-maze and in the Morris water maze (MWM) for memory evaluation. In the plus-maze, each mouse was placed at the end of an open arm and initial freezing and the time to enter into an enclosed arm (transfer latency) were measured. SW mice decreased both measures over repeated trials, whereas no decrease of freezing was observed in CO mice, thus suggesting increased emotionality in this group. Compared to CO mice, TS mice showed less initial freezing, shorter transfer latencies, and spent less time in enclosed arms, suggesting a reduced ability to habituate or to inhibit behaviour. Animals were also submitted to a learning-set paradigm consisting of reaching a new platform position each day in the MWM. Two training phases (separated by a resting period of 6 weeks), each including eight acquisition and four cued sessions, were performed (each session consisting of four pairs of trials). CO and SW mice already reached an asymptotic performance by the second day of the first phase whereas TS mice did not achieve that level until the second training phase. The progression over trials indicated that CO and SW animals learned the new platform position between trials 1 and 2 of each session, whereas TS animals failed to do it and had more difficulties to find the platform when it was placed in the centre of the pool as compared to the other positions (SW, NE, E). The results suggest that TS mice show working memory impairments in addition to long-term memory deficits, although extensive training appeared to facilitate TS mice to achieve a level of performance similar to their control littermates. This represents another aspect of the cognitive deficits shown by TS mice: a mouse model of the human Down syndrome.

Animals↗
PubMed1997

Neonatal handling and environmental enrichment effects on emotionality, novelty/reward seeking, and age-related cognitive and hippocampal impairments: focus on the Roman rat lines.

Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats are selected and bred for extreme divergence in two-way active avoidance acquisition. In addition, compared to RLA/Verh rats, RHA/Verh rats are (behaviorally and physiologically) less anxious or reactive to stressors, show increased novelty (sensation)-seeking behavior as well as a higher preference for rewarding substances, and are usually less efficient in learning tasks not involving shock administration. The present article reviews evidence showing that neonatal handling and/or environmental enrichment leads to enduring effects (their magnitude frequently depending upon the rat line) on those behaviors. For example, it has been found that neonatal handling reduces most of the (behavioral and physiological) signs of emotionality/anxiety in RLA/Verh rats, while environmental enrichment increases their novelty seeking (also the case with RHA/Verh rats), saccharin and ethanol intake, and sensitivity to amphetamine. Finally, initial results (currently being further elaborated upon) support a preventive action of both environmental treatments on age-related impairments in learning a spatial, water maze task as well as on hippocampal neuronal atrophy.

Animals↗
PubMed1997

Labyrinth exploration, emotional reactivity, and conditioned fear in young Roman/Verh inbred rats.

An inbreeding program has been carried out with the Swiss sublines of Roman high- and low-avoidance rats since 1993. The present study reports the first experiments conducted with young animals of those inbred strains (RHA-I/Verh and RLA-I/Verh, respectively) from the sixth and seventh inbreeding generations. The results confirmed expected behavioral profiles. Compared to the RHA-I/Verh strain, RLA-I/Verh rats showed decreased entries into the illuminated central arena of an hexagonal tunnel maze, as well as decreased spontaneous locomotor activity and increased defecations, in two independent experiments. Young RLA-I/Verh females explored less than did their RHA-I/Verh counterparts during session 1 of a conditioned-fear experiment preceding shock administration, and in session 2 (conducted 24 h after the application of three footshocks), they showed greater conditioned behavioral inhibition (i.e., reduced amount of rearing), as well as higher defecation scores, than did RHA-I/Verh females.

Analysis of Variance↗
PubMed1996

Effects of postnatal handling of rats on emotional, HPA-axis, and prolactin reactivity to novelty and conflict.

The present studies evaluated whether or not postnatal handling (PH) (administered during the first 21 days of life) could enduringly improve coping behavior with novel and/or conflict situations. To this purpose, different groups of naive male rats (control and PH-treated) were submitted in separate experiments to 1 of the 3 following situations: an emotional reactivity test (in 4-month-old animals), an open-field session followed by endocrine measurements (in 7-month-old animals) and a punished drinking test (in 11-month-old animals). PH effects were significant in the 3 situations: handled animals were less resistant to capture or to the handling manouvers involved in the emotional reactivity test: the hormonal responses (corticosterone, prolactin, and ACTH changes) during and after an open-field stress were less intense, and PH effects lasted up to 11 months in the punished drinking test, as measured by a higher number of punished responses and less time spent freezing by handled animals during the punished period. The results are discussed in relation to previous evidence showing a long-lasting reduction of fearfulness in rats due to postnatal handling.

Adrenocorticotropic Hormone↗
PubMed1996

Evaluation of perinatal flumazenil effects on the behavior of female RLA/Verh rats in anxiety tests and shuttle box avoidance.

The present study investigated the effects of perinatal flumazenil (Ro 15-1788, a benzodiazepine receptor antagonist), given from gestational day 15 to the 14th day after giving birth, at two doses (3.5 and 6.3 mg/kg/ day) on the behavior of female RLA/Verh rats. This rat line has been selectively bred for non-acquisition of two-way active avoidance. Offspring of treated/non-treated dams were tested when adults for two-way active (shuttle box) avoidance acquisition. For comparison reasons additional offspring coming from the same treatments were used in an hyponeophagia test and in both an open field and a plus maze tests. The results show that perinatal flumazenil, specially the lower dose (and also the highest dose, although only in the final phases of the shuttle box training) was able to improve two-way active avoidance acquisition, as it has been previously found with males, whereas it failed to show any effect in the hyponeophagia task, the open field and the plus-maze tests. As two-way active avoidance acquisition can be enhanced both by reducing emotionality/anxiety or by improving memory, it is suggested that flumazenil treatment could have affected either one or both processes.

Animals↗
PubMed1995

A behavioral assessment of Ts65Dn mice: a putative Down syndrome model.

Mice which are trisomic for only the human chromosome (Chr) 21-homologous segment of mouse Chr 16 (segmental trisomy), including a portion of the Down syndrome region of human Chr 21, have recently been developed. Since these segmentally trisomic mice, designated Ts(17(16))65Dn, survive to adulthood, they may represent a mouse model for the study of Down syndrome. A partial characterization of their behavioral phenotype was undertaken by evaluating the sensorimotor reflexes, exploration, locomotor activity, emotionality and spatial learning in 16 male Ts65Dn mice (TS) and 16 control (CO) littermates. No sensorimotor deficits appeared in TS compared to CO mice. By contrast, head-dipping behaviour in the hold board was increased in TS mice with respect to the CO group, showing a higher repetition rate of previously explored holes. Crossings in the open field and total arm entries in the plus maze were higher in TS than in the CO group during the dark phase of the light-dark (LD) cycle under red light, but not during the light phase of the LD cycle under white light. Entries into the open arms of the plus maze were increased overall in TS mice when compared to CO mice, but no differences were found in time spent in the open arms. TS mice showed impaired place learning in the Morris water maze, whereas they were able to reach the same performance as CO animals in cued learning. Thus, absence of sensorimotor deficits, increased exploration, hyperactivity under certain experimental conditions and a moderate impairment of spatial learning were the principal characteristics observed in TS mice compared to their CO littermates.

Animals↗
PubMed1995

Early environmental stimulation produces long-lasting changes on beta-adrenoceptor transduction system.

Long-term behavioral and biochemical effects of exposure to differential early stimulation (postnatal handling and/or enriched environment) were studied in 18- to 20-month-old Sprague-Dawley rats. Postnatal handling treatment was given between 1 and 22 postnatal days. In the enriched environment procedure, the pups were maintained under enriched conditions from weaning until postnatal Day 100. At 18 months of age animals were tested for working memory in an object recognition test, based on the differential exploration of familiar and new objects. Animals reared in the enriched environment performed better in the working memory test than did control or postnatally handled rats. No interaction was observed between postnatal handling and environmental enrichment on cognitive parameters. At 20 months of age, the animals were sacrificed and cyclic AMP formation was determined under basal conditions and after activation of beta-adrenoceptors in cerebral cortex and hippocampus. Both postnatal handling and its combination with exposure to enriched environment significantly increased basal cyclic AMP accumulation in cerebral cortex, but not in the hippocampus. Environmental enrichment was able to induce a long-lasting modification in the responsiveness of the beta-adrenergic neurotransmitter system as reflected by a decreased cyclic AMP accumulation after beta-adrenoceptor activation by means of isoprenaline, in either anatomical structure. It is suggested that manipulations of the environment early in life leading to a reduction in age-related memory deficits produce subtle but long-lasting modifications of noradrenergic transmission.

Animals↗
PubMed1995

Effects of prenatal diazepam on two-way avoidance behavior, swimming navigation and brain levels of benzodiazepine-like molecules in male Roman high- and low-avoidance rats.

Utilizing psychogenetically selected Roman high- and low-avoidance rats (RHA/Verh and RLA/Verh), the present experiments investigated the effects of prenatally administered vehicle and diazepam (1 and 3 mg/kg per day, SC) on the behavior and neurochemistry of adult, male offspring. Active, two-way avoidance behavior was analyzed in 96 rats, at 6 months of age, and swimming navigation in 68 others, at 11 months. Three weeks after testing, selected brain areas from the latter animals were immunoassayed for benzodiazepine (BZD)-like molecules. The 3 mg/kg dose of diazepam both decreased freezing behavior in the shuttle box and reduced the hippocampal content of BZD-like molecules in the RLA/Verh male rats. Swimming navigation (spatial learning), at which the RLA/Verh rats were more adept, was not specifically affected by prenatal diazepam in either rat line. The possibility exists that an increased hippocampal release of BZD-like substances may be necessary to alter shuttle box behavior in RLA/Verh rats.

Animals↗
PubMed1995

Postnatal handling reduces emotionality ratings and accelerates two-way active avoidance in female rats.

The present study evaluated whether postnatal handling (PH; administered daily during the first 21 days of life) could reduce anxiety or emotional reactivity in tasks of either spontaneous or conditioned fear-related behavior. To this purpose control nonhandled and postnatally handled female rats were submitted to three different behavioral tests: an emotionality rating (ER) followed by an elevated plus-maze test of anxiety in one experiment, and an acquisition of two-way active (shuttlebox) avoidance under two different training conditions in a separate experiment. Significant effects of PH treatment appeared in the three testing situations, clearly indicating an important and enduring reduction of emotionality/anxiety in PH-treated rats. Of special interest were the results of shuttlebox training: by shortening the conditioned stimulus (CS) and the intertrial interval (ITI) duration, avoidance acquisition was impaired as expected but the improving effects of PH were even more marked. The results are discussed in relation to previous studies reporting controversial results in the same (or similar) testing situations.

Animals↗
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↗