Low-avoidance Rats Research Articles

Male Hatano High-Avoidance Rats Show High Avoidance and High Anxiety-Like Behaviors as Compared with Male Low-Avoidance Rats

Our prime objective was to establish an optimal model animal for studying avoidance learning and memory in rodents. The two-way rat inbred strains of Hatano high- (HAA) and low-avoidance (LAA) animals were originally selected and bred in accordance with their high or low performance respectively in the shuttle-box active avoidance task. Previous studies demonstrated that they have clear strain differences in endocrine stress response, which is related to acquisition of aversive learning and emotional reactivity. To evaluate the effect of selection by the shuttle-box task on avoidance performance and emotional reactivity, male Hatano rats underwent passive avoidance, open field and elevated plus maze tests. The present results show that the avoidance performance in the passive task was significantly greater in HAA rats than in LAA rats. Furthermore, HAA rats showed high anxiety-like behaviors compared with LAA rats in open field and elevated plus maze tests. Taken together, this study demonstrated that 1) selection and breeding of Hatano HAA and LAA strain rats by shuttle-box task had been properly carried out with the criterion of high and low avoidance performance respectively and that 2) HAA rats were predisposed to high anxiety compared with LAA rats. These results indicated that Hatano HAA and LAA rats can be useful models for studying avoidance learning and memory.

Impulsivity and aggressive behavior in Roman high and low avoidance rats: Baseline differences and adolescent social stress induced changes

Adverse and stressful experiences during adolescence are often of a social nature. The social defeat model in rats is used as an animal model for bullying in humans. Usually large individual differences in response to social defeat are found. The personality type that is mostly affected and the underlying mechanisms are unknown. We used male rats of the Roman selection lines to test whether social defeat (between postnatal days 45 and 57) followed by social isolation has a different impact in animals with divergent levels of emotional reactivity and coping style. The level of offensive aggression, impulsivity and performance during frustrating non-reward (extinction) were used as measures for the adult coping style of animals. Impulsivity was measured by performance on an unpredictable operant conditioning schedule (variable interval-15, VI-15) for food reinforcement.This study demonstrates that the adult, baseline level of impulsivity is higher in Roman high avoidance (RHA) rats. RHA rats showed a higher number of lever presses compared to Roman low avoidance (RLA) rats on a VI-15 schedule. The level of offensive aggression did not differ between the two lines. Surprisingly, a tendency towards more offensive aggression in RLA rats was found.Social stress during adolescence disturbed the normal development of adult personality, mostly in RHA rats. RHA rats that were defeated during adolescence reduced the number of lever presses on the VI-15 schedule of reinforcement and were more persistent during a session of frustrating non-reward. However, we did not find an effect of social defeat on performance during extinction. A tendency towards increased attack latencies after social defeat in adolescence was found. The time spent on offensive aggression was unaffected by social defeat.

Individual variation in the (patho)physiology of energy balance

There are large individual differences in the susceptibility for metabolic disorders such as obesity, the metabolic syndrome and type 2 diabetes. Unfortunately, most animal studies in this field ignore the importance of individual variation which limits the face validity of these studies for translation to the human situation. We have performed a series of studies that were particularly focused on the individual differences in the (patho)physiology of energy balance. The studies were performed with passive and proactive individuals of two different rat strains: the Roman High and Low Avoidance rats and the Wild type Groningen rat. The data reveal that passive and proactive individuals differ significantly on several parameters, i.e. body composition, Hypothalamic-Pituitary-Adrenal (HPA) axis activity, plasma levels of insulin and leptin, intestinal transit time, systolic blood pressure and meal patterns. We also found that the selection line of the Roman Low Avoidance rat may be considered as a non-obese animal model for the metabolic syndrome, since these rats display, under sedentary conditions, many of the related symptoms such as hypertension, visceral adiposity and insulin resistance during an intravenous glucose tolerance test. These symptoms disappeared when the animals were allowed to exercise voluntarily in a running wheel. We conclude that experiments with passive and proactive individuals are highly relevant for studying the (patho)physiology and behavior of energy balance and the related metabolic disorders.

Endocrine Mechanisms Responsible for Different Follicular Development During the Estrous Cycle in Hatano High- and Low-avoidance Rats

Hatano high- and low-avoidance rats (HAA and LAA strains, respectively) were selected and bred according to the avoidance rate in a shuttle-box task. Although they have clear strain differences in ovarian function, their endocrine mechanisms still remain to be clarified. Differences in female reproductive endocrinology between the strains were investigated by means of measuring the plasma concentration of reproductive hormones during the estrous cycle. LAA rats showed approximately threefold lower basal and surge levels of LH, a more than fourfold lower level of FSH surges and higher levels of inhibin A and inhibin B during the estrous cycle compared with the levels seen in HAA rats. The concentration of estradiol-17β in the proestrous stage was significantly lower in LAA rats than in HAA rats. Additionally, LH and FSH secretions from primary cultured anterior pituitary cells with or without in vitro GnRH stimulation were lower in the cells derived from LAA rats and, in terms of FSH secretion, were unresponsive to GnRH in contrast to cells derived from HAA rats. Although an increased number of preantral follicles in diestrus were observed in LAA rats, number of hCG-induced ovulation was lower in LAA rats. LAA rats may have much more follicle growth during the early stage of folliculogenesis, but most follicles might not grow into mature follicles. These results strongly suggest that the strain difference in ovarian function of these two Hatano rats is due to the difference in the regulation of hypothalamo-hypophyseal system for gonadotropins secretion.

Endocrinological Differences between Hatano High- and Low-Avoidance Rats during Early Two-Way Avoidance Acquisition

Hatano high (HAA)- and low (LAA)-avoidance rats were selected from Sprague-Dawley rats genetically on the basis of their active avoidance behavior in a shuttle-box test. The purpose of this study was to investigate stress-related alterations of hormones corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP), prolactin, and adrenocorticotropin (ACTH) in the brain and blood during early avoidance acquisition using two lines of Hatano rats. In paraventricular nucleus (PVN) of the hypothalamus, the CRH levels in HAA rats were significantly increased after shuttle-box tasks compared with before the tasks, whereas the CRH levels in LAA rats significantly decreased after shuttle-box tasks compared with before the tasks. In the HAA rats, the CRH and AVP levels in the median eminence decreased after shuttle-box tasks, whereas there were no significant differences in the levels between before and after shuttle-box tasks in LAA rats. The plasma concentrations of ACTH were significantly higher in HAA rats than in LAA rats after shuttle-box tasks. These results show that the response of CRH-ACTH was higher in HAA rats than in LAA rats. This phenotype may be an important reason for the high avoidance rates of shuttle-box tasks in HAA rats. These endocrine differences in early avoidance acquisition may be involved in regulation of their avoidance responses in the shuttle-box task.

The frequency and power of theta band recorded from dorsal CA1 field of hippocampus are related to individual differences in emotional reactivity of the Roman High (RHA/Verh) and Low Avoidance (RLA/Verh) rats

The frequency and power of theta band recorded from dorsal CA1 field of hippocampus are related to individual differences in emotional reactivity of the Roman High (RHA/Verh) and Low Avoidance (RLA/Verh) rats

One-way avoidance learning in female inbred Roman high- and low-avoidance rats: Effects of bilateral electrolytic central amygdala lesions

Female inbred Roman high- (RHA-I) and low- (RLA-I) avoidance rats show differences in one-way avoidance learning only when the task implies a highly aversive situation (1 s in the “non-shock”-associated safe compartment, as opposed to 30 s). These between-strain differences seem to depend on strain differences in emotionality, given that: (i) they are abolished by IP administration of the GABAergic anxiolytic diazepam (Torres et al. [32]) and (ii) avoidance responding appears to correlate with cellular density in the basolateral amygdala (Gómez et al. [9]). In the present study we further analyzed whether the implication of the amygdala in one-way avoidance depends on the experimental situation aversiveness (30 s vs. 1 s in safety). After bilateral electrolytic lesions (1 mA; 20 s) of the central amygdala (CeA), RHA-I and RLA-I rats were exposed to a danger compartment (where they received a warning signal – 88 dB tone – followed by a 1 mA electric foot-shock), and a safe compartment, where these stimuli were not presented. The number of trials needed to reach 5 consecutive avoidance responses was used as dependent variable. Sham lesioned RLA-I rats showed poorer performance than sham lesioned RHA-I rats only under the 1 s condition. The CeA lesion disrupted the avoidance response only in 1 s groups, abolishing the between-strain performance differences observed under this condition. These results indicate the implication of CeA in one-way avoidance performance, and suggest a reciprocal modulation of fear and reinforcement (i.e. fear relief) in this form of aversive learning.

Impulsivity characterization in the Roman high- and low-avoidance rat strains: behavioral and neurochemical differences.

The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats for rapid vs extremely poor acquisition of active avoidance behavior in a shuttle-box has generated two phenotypes with different emotional and motivational profiles. The phenotypic traits of the Roman rat lines/strains (outbred or inbred, respectively) include differences in sensation/novelty seeking, anxiety/fearfulness, stress responsivity, and susceptibility to addictive substances. We designed this study to characterize differences between the inbred RHA-I and RLA-I strains in the impulsivity trait by evaluating different aspects of the multifaceted nature of impulsive behaviors using two different models of impulsivity, the delay-discounting task and five-choice serial reaction time (5-CSRT) task. Previously, rats were evaluated on a schedule-induced polydipsia (SIP) task that has been suggested as a model of obsessive-compulsive disorder. RHA-I rats showed an increased acquisition of the SIP task, higher choice impulsivity in the delay-discounting task, and poor inhibitory control as shown by increased premature responses in the 5-CSRT task. Therefore, RHA-I rats manifested an increased impulsivity phenotype compared with RLA-I rats. Moreover, these differences in impulsivity were associated with basal neurochemical differences in striatum and nucleus accumbens monoamines found between the two strains. These findings characterize the Roman rat strains as a valid model for studying the different aspects of impulsive behavior and for analyzing the mechanisms involved in individual predisposition to impulsivity and its related psychopathologies.

Prolactin induces phosphorylation of the STAT5 in adrenal glands of Hatano rats during stress

Aims To investigate the signaling of prolactin (PRL) in the adrenal gland during stress in Hatano high- (HAA) and low-avoidance (LAA) rats. Main methods Adrenal glands of both strains were collected at 0, 15 and 30 min after stress. The protein levels of phosphorylated STAT5 and the mRNA levels of melanocortin receptor 2 (MC2R) and PRL receptor (PRLR) were analyzed. Furthermore, the effects of bromocriptine-induced hypoprolactinemia on adrenocortical responses to stress were investigated. Key findings Adrenocorticotropic hormone (ACTH) concentrations in HAA were greater than LAA, while the difference in PRL concentrations were found only at 120 min after stress induction. No strain differences were observed in corticosterone or progesterone in response to stress. The stress-induced increase in MC2R mRNA expression was higher in HAA, but there was a lowered PRLR mRNA expression. STAT5 become highly phosphorylated in response to stress in both strains, but bromocriptine led to a reduction the STAT5 phosphorylation. Exposure to bromocriptine was associated with a reduction in plasma PRL in response to stress in both strains, while the ACTH levels were not altered. However, the decrease in corticosterone and progesterone in response to stress was observed only in bromocriptine-treated LAA rats. Significance These data show that PRL plays an important role in the regulation of corticosterone and progesterone release in LAA but not in HAA during stress. These results suggest that PRL increase in response to stress, and it acts on the adrenal cortex and thereby plays an important physiologic role in protecting against acute stress.

The passive coping Roman Low Avoidance rat, a non-obese rat model for insulin resistance

The aim of the study was develop to an animal model that links coping style to insulin resistance. We hypothesized that the psychogenetically selected Roman Low Avoidance (RLA) rats may serve as such a model. To test this hypothesis, we submitted both RLA and Roman High avoidance (RHA) rats to a series of intravenous glucose tolerance tests (IVGTT). These IVGTT were followed by post mortem metabolic characterization of the selection lines. It was found that plasma insulin levels are markedly elevated in the passively coping RLA rat, both in baseline conditions and during the intravenous glucose tolerance tests. The elevation in plasma insulin was accompanied with increased levels of plasma corticosterone, FFA, leptin and triglycerides but not by changes in body weight. We conclude that the passive, highly emotional RLA rat is metabolically different from both the RHA rat and the standard control Wistar rat and may serve as a non-obese animal model for insulin resistance.

P.4.11 Higher histamine synthesis and release in inbred Roman high versus low avoidance rats: a histaminergic hypothesis

ethanol (1 g/kg) or WIN 55,212-2 was administered for 5 days, from PND 28 to PND 32. Such early ethanol exposure decreased (−28% p< 0.05) spontaneous alcohol consumption at adulthood. In contrast, their spontaneous alcohol intake increased (+37% p< 0.05) when C57BL/6J mice had been treated with WIN 55,212-2 at adolescence. In DBA/2J mice, which spontaneously avoid alcohol at adult age, the latter treatment did not significantly affect this behavioural trait. In contrast, early alcohol intake at adolescence regularly increased their spontaneous alcohol consumption under free-choice conditions at adulthood. This augmentation ranged between +34% and +94% (p< 0.001), depending on the dose and duration of early ethanol administration. No changes in 5-HT1A G protein coupling efficacy were generally observed in animals which had been exposed to alcohol at adolescence, except in C57BL/6J mice with an induced decrease in alcohol intake at adulthood (see above) for which 5-carboxamidotryptamine exhibited a 3-fold increased potency (p< 0.05) to enhance [35S]GTP-g-S binding in the hippocampus. These results show that early ethanol and/or cannabis consumption can affect ethanol preference at adulthood. The differences between C57BL/6J and DBA/2J mice indicate that such induced modulations of alcohol intake are under genetic control. The change in 5-HT1A receptor coupling suggests that the critical influence of gene– environment interactions on alcohol preference/avoidance at adulthood may depend-in part-on serotoninergic mechanisms. This research has been supported by grants from INSERM, IREB and MILDT.

Effects of Transmaternal Exposure to Genistein in Hatano High- and Low-Avoidance Rats

Hatano high- and low-avoidance (HAA and LAA) rats are separated by breeding from Sprague-Dawley rats by high versus low rates of avoidance responses in a shuttle-box task. In addition, compared to HAA rats, LAA rats show lower running-wheel activity, later sexual maturation, 5-day estrous cycling, lower sperm motility, more pronounced immunological reactions, and are generally less reactive to stress. The present study was designed to compare the effects of transmaternal exposure to genistein on these characteristics between HAA and LAA rats. To this aim, litters from both strains were fostered onto Sprague-Dawley rats receiving genistein by gavage with 5 mg/animal/day from day 17 of pregnancy through day 21 of lactation. Inhibited growth after weaning and reduced uterine weight at weaning were observed in the LAA offspring reared by genistein-treated dams. IgM antibody production in response to sheep red blood cells was significantly decreased in the HAA offspring reared by genistein-treated dams. During restraint stress, the plasma concentration of corticosterone was significantly lower in the LAA offspring reared by genistein-treated dams. Strain-related differences were detected in shuttle-box avoidance performance, running-wheel activity, estrous cycling, and sperm motility. The results demonstrate that transmaternal exposure to genistein potentially affects the immunological and stress responses as well as the post-weaning growth of the offspring. It suggests that a comparative study using Hatano rats would be useful for studying the influence of endocrine active chemicals on the whole body systems.

Differences in adrenocortical secretory and gene expression responses to stimulation in vitro by ACTH or prolactin between high- and low-avoidance Hatano rats

Rats of the Hatano high-avoidance (HAA) and low-avoidance (LAA) strains have been genetically selected on the basis of their two-way active avoidance behavior, and have different endocrine responses to stress. The present study focused on the adrenal steroid hormone responses of the Hatano strains and identifies differences in regulation of the adrenal cortex in vitro of HAA and LAA rats. Although incubation with prolactin (PRL) and/or adrenocorticotrophic hormone (ACTH) resulted in a dose-dependent increase of corticosterone and progesterone release by adrenal cells from both HAA and LAA male rats, the responses were markedly increased for adrenal cells from LAA rats as compared with HAA rats. This finding suggested that adrenal glands of HAA rats are less sensitive to PRL and/or ACTH than adrenals from LAA rats. Several possible intra-adrenal regulators were investigated. The basal level of expression of steroidogenic acute regulatory protein (StAR) and the long form of the PRL receptor (PRLR-L) mRNAs was higher in adrenals of LAA rats. ACTH treatment of adrenal cells from HAA rats resulted in statistically significant increases in melanocortin receptor 2 (MC2R) mRNA expression, while neither ACTH nor PRL altered MC2R mRNA expression in adrenal cells of LAA rats. Conversely, the increase in PRLR-L mRNA expression induced by PRL was observed only in adrenal cells from LAA rats. Treatment of adrenal cells with PRL and/or ACTH increased the expression of StAR and CYP11A1 mRNAs for both Hatano strains. However, the induction of StAR mRNA expression was higher in LAA rats, but the CYP11A1 response was lower. These findings indicate that adrenal cells of the LAA strain have higher sensitivity to secretagogues than those of the HAA strain. These results suggest that PRL may also be important in stimulating secretion of adrenal steroid hormones.

One-way avoidance acquisition and cellular density in the basolateral amygdala: Strain differences in Roman high- and low-avoidance rats

The goal of the present experiment was to study the performance of inbred Roman high- (RHA-I) and low- (RLA-I) avoidance rats in one-way avoidance learning and to relate the behaviour of the animals to cellular density in the basolateral amygdala (BLA), a brain region related to fear and anxiety. Thus, females from both strains were exposed either to 30 s or 1 s in the safe place as a function of experimental condition, until they reached five consecutive avoidance responses. Thereafter, the rats were perfused, and their brains sectioned in 40 μm coronal sections, stained with cresyl violet. The area (percentage of field) corresponding to the BLA structures was quantified by computerized-assisted image analysis. The results indicated that RLA-I showed a significantly poorer acquisition of the one-way avoidance task than did RHA-I rats, but only when safe time was the shortest (1 s). In addition, the number of trials needed to reach the behavioural acquisition criterion was negatively correlated with BLA cellular density in RLA-I rats. These data suggest the possibility of relating behavioural and neuro-anatomical indexes, enabling exploration of the biological basis of fear/anxiety behaviours.

Diverse Sensitivity of RHA/Verh and RLA/Verh Rats to Emotional and Spatial Aspects of a Novel Environment as a Result of a Distinct Pattern of Neuronal Activation in the Fear/Anxiety Circuit

Psychogenetically selected Roman high (RHA/Verh) and Roman low (RLA/Verh) avoidance rats constitute a well-recognized model of diverse emotional reactivity. The two Swiss lines display marked behavioral and endocrine differences in reaction to a novel environment. In our study we found that these differences are accompanied by a distinct, line-specific pattern of neuronal activation within the fear/anxiety circuit. We have compared the c-Fos protein expression in the medial prefrontal cortex (mPFC), basolateral (BLA), central (CeA), medial (MeA), and cortical (CoA) nuclei of amygdala, paraventricular nucleus of the hypothalamus (PVN), and CA1, CA2, and CA3 fields of the hippocampus upon exposure to a novel situation of different stressorgeneity (open field with illuminated center, elevated plus maze, hole board test and acute restraint). Profound between-line differences in the sensitivity to emotional and spatial aspects of the behavioral challenge were observed for tests measuring spontaneous behavior. This effect seems to reflect different motivational factors driving the rat behavior, which clearly suggests that the diverse emotional reactivity of RHA/Verh and RLA/Verh rats is a result of different activation of the fear/anxiety circuit.

The partial reinforcement extinction effect (PREE) in female Roman high- (RHA-I) and low-avoidance (RLA-I) rats

The present experiment was designed with the goal of studying the partial reinforcement extinction effect (PREE) in female inbred Roman high- (RHA-I) and low-avoidance (RLA-I) rats. Two groups of RHA-I and two of RLA-I food-deprived animals were placed in a straight alley where they were partially or continuously reinforced. Once the animals reached the acquisition criterion, they were exposed to an extinction phase where the reinforcement was omitted. During the extinction phase RHA-I animals continuously reinforced during acquisition exhibited more resistance to extinction than their RLA-I counterparts, whereas only RLA-I rats partially reinforced during acquisition showed an increased resistance to extinction in comparison to continuously reinforced control RLA-I rats, this PREE being absent in RHA-I animals. These results are discussed within the framework of PREE theories that account for this effect by using emotional mechanisms, as pertains to the repeatedly observed RHA–RLA differences in emotional reactivity.

The Roman High- and Low-Avoidance Rat Lines Differ in the Acquisition, Maintenance, Extinction, and Reinstatement of Intravenous Cocaine Self-Administration

The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats for, respectively, rapid vs extremely poor acquisition of avoidant behavior in a shuttlebox has produced two phenotypes that differ in temperament traits, in mesocortical/mesolimbic dopamine system function, and in the behavioral and neurochemical responses to the acute and repeated administration of psychostimulants and opiates. The phenotypic traits of the RHA line predict higher susceptibility, compared with RLA rats, to the reinforcing properties of addictive substances like cocaine. The present study was designed to compare the acquisition, maintenance, reinstatement of drug-seeking after long-term extinction, and reacquisition of intravenous cocaine self-administration (SA) behavior in the Roman lines. Compared with RLA rats, the rates of responding during cocaine SA acquisition were higher, extinction from cocaine SA was prolonged, and drug-induced reinstatement of cocaine-seeking behavior was more robust in RHA rats. Moreover, only RHA rats reacquired extinguished lever-pressing activity when a low reinforcing dose of cocaine was available. These findings are consistent with the view that subjects with genetically determined high responsiveness to the acute and chronic (ie, sensitizing) effects of psychostimulants, such as RHA rats, also display a higher propensity to self -administer cocaine. Further comparative studies in the Roman lines, using SA paradigms that distinguish mere drug-taking from the compulsive and uncontrolled drug use that characterizes addiction in humans, may eventually help to characterize the relationships among genotype, temperament traits, and neurobiological mechanisms involved in the individual vulnerability to cocaine addiction.

Divergent effect of the selective D3 receptor agonist pd-128,907 on locomotor activity in Roman high- and low-avoidance rats: relationship to NGFI-A gene expression in the Calleja islands

The inbred Roman high- (RHA-I) and low-avoidance (RLA-I) rats, differing in dopaminergic activity and novelty/substance-seeking profiles, may be a suitable model to study the implication of the dopaminergic system in vulnerability to drug abuse. Differences in D3 receptor binding recently described between the two strains (Guitart-Masip M, Johansson B, Fernández-Teruel A, Cañete T, Tobeña A, Terenius L, Giménez-Llort L, Neuroscience 142:1231-1243, 2006b) may be important in shaping the aforementioned differences in novelty seeking. The aim of the present work was to study the effect of D3 receptor activation on novelty-induced locomotor activity in these two strains of rats. We administered saline and PD-128,907 (0.01 and 0.1 mg/kg), a putative D3 receptor agonist, to the Roman rats and studied the locomotor activity when animals were placed in a novel environment. Thereafter, by means of in situ hybridization, nerve growth factor inducible clone A (NGFI-A) mRNA was measured in the striatum and the Calleja islands of these animals. We found that RLA-I rats showed stronger locomotor inhibition than RHA-I rats after PD-128,907 administration. Moreover, RLA-I rats showed stronger reduction of NGFI-A mRNA in the Calleja islands than RHA-I rats. These results, together with previous findings, suggest that differences in D3 receptor expression in the Calleja islands may contribute to the divergent behavioral effect of PD-128,907 administration in the two strains of Roman rats.

Regional adaptations in PSD-95, NGFI-A and secretogranin gene transcripts related to vulnerability to behavioral sensitization to amphetamine in the Roman rat strains

Genetically selected for high or low two-way active avoidance, Roman high-avoidance (RHA) and Roman low-avoidance (RLA) rats differ in their central dopaminergic activity, sensation/novelty- and substance-seeking profiles. These animals are, therefore, well suited to identify anatomical and neurochemical concomitants of behavioral sensitization, a phenomenon linked to addictive liability. We submitted inbred RHA (RHA-I), inbred RLA (RLA-I) and Sprague–Dawley-OFA (SD-OFA) rats to a sensitization regimen with amphetamine and studied the behavioral response to an amphetamine challenge after a 2-week withdrawal period. The expression patterns of nerve growth factor inducible clone A (NGFI-A), secretogranin, post-synaptic density protein of 95 Kd (PSD-95), prodynorphin and proenkephalin mRNA were also analyzed using in situ hybridization, after the challenge with amphetamine. RHA-I rats showed stronger sensitization than SD-OFA rats. RLA-I rats did not show sensitization but were hyper-reactive to amphetamine. Expression of behavioral sensitization in RHA-I rats activated secretogranin and PSD-95 mRNA in the nucleus accumbens core. On the other hand, high induction of NGFI-A mRNA in the central amygdala was observed in RLA-I rats when they experienced amphetamine for the first time in the challenge. Our results reveal that 1) the acute locomotor response to amphetamine does not predict vulnerability to behavioral sensitization and 2) differences in vulnerability to sensitization may involve distinctive cellular adaptations at particular brain locations which may be related to addictive vulnerability.

One-way avoidance learning and diazepam in female roman high-avoidance and low-avoidance rats

The goal of this experiment was to study the influence of the time spent in the safe compartment (30 vs. 1 s) and of an intraperitoneal injection of diazepam (1 mg/kg vs. vehicle) on one-way avoidance learning, in inbred female roman high-avoidance and roman low-avoidance rats. Rats learned to run from a danger compartment, where they received a warning signal (88 dB tone) followed by a 1 mA electric footshock, to a safe compartment, where these stimuli were not presented. The number of trials needed to reach 10 consecutive avoidance responses was the dependent variable. Roman low-avoidance rats exposed to 1 s in the safe compartment showed poorer performance than their roman high-avoidance counterparts. These differences were not observed in rats exposed to 30 s in the safe place, and were abolished by the injection of diazepam. These results suggest the importance of fear and reinforcement in one-way avoidance learning and its usefulness for studying emotional processes underlying genetic or pharmacological manipulations.