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The behavioral response to novelty is altered in rats neonatally exposed to cocaine.

It has recently been suggested that the effects of in utero cocaine exposure may result in subtle deficits related to a challenging environment, including exposure to novelty or stress. This study used a neonatal drug-exposure model to examine the behavioral response to a novel environment in rodents. Subjects were artificially reared (AR) from postnatal Days 4-10. There were four treatment groups; AR 40 mg/kg/day cocaine, AR 20 mg/kg/day cocaine, AR control group receiving no drug, and a normally reared control. In Experiment 1, subjects were tested for their preference of maternal home-cage or clean wood-chip odors in a T-maze on postnatal Day 15. Subjects from all treatment groups preferred the maternal odor. In Experiment 2, subjects were habituated to four familiar odors and tested with a novel odor in an open field (postnatal Days 16-21). Neonatal exposure to 20 mg/kg/day cocaine led to an overall increase in exploratory behavior during testing, whereas 40 mg/kg/day did not, supporting the hypothesis that developmental exposure to cocaine at some doses may alter the offspring's response to a changing environment.

Animals↗

[Effect of amino acid derivatives of beta-carboline-3-carboxylate on rat behavior].

It was shown, that administration of methyl ether N-(beta-carboline-3-carbonyl)-glycine (GA) at dose level of 1-10 mg/kg markedly reduced exploratory behavior and motor activity in the open field test and facilitated manifestation of different rats defend reaction types. Methyl ether N-(beta-carboline-3-carbonyl)-leucine (LA) at the same doses was less effective. Besides GA (10 mg/kg) like earlier described anxiogenic compound FG 7142 suppressed isolation induced muricide behavior of rats. The results obtained combined with literary data allow us to conclude, that GA possesses expressed anxiogenic activity.

Aggression↗

Behavioral profile of raclopride in agonistic encounters between male mice.

Raclopride is a substituted benzamide with high selectivity as an antagonist of central dopaminergic D2 receptors and potential antipsychotic effects. In comparison with a classic DA receptor blocking agent like haloperidol, raclopride displays an atypical profile in preclinical tests for extrapyramidal side effects. Antiaggressive properties of raclopride on agonistic behavior have not yet been fully explored. In this work the effects of raclopride (0.1, 0.3, or 0.6 mg/kg) on aggressive and motor behaviors in male mice were studied. Aggression tests were performed 30 min after injections. Encounters were videotaped and behavior was evaluated, measuring the time spent in 11 broad categories of behavior. The results show a clear antiaggressive effect of raclopride, with very little motor impairment and some increase in exploratory behavior. This behavioral profile is very similar to the one observed with other atypical neuroleptics and differs somewhat from that found in the classic compounds.

Agonistic Behavior↗

Activation of protein kinase B/Akt in the periphery contributes to pain behavior induced by capsaicin in rats.

Protein kinase B (PKB/Akt) is a member of the second-messenger regulated subfamily of protein kinases. It is implicated in signaling downstream of growth factors, insulin receptor tyrosine kinases and phosphoinositide 3-kinase (PI3K). Current studies indicate that nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and PI3K help mediate inflammatory hyperalgesia. However, little is known about the role of PKB/Akt in the nociceptive system. In this study, we investigated whether PKB/Akt in primary sensory neurons is activated after noxious stimulation and contributes to pain behavior induced in rats by capsaicin. We demonstrated that phospho-PKB/Akt (p-PKB/Akt) is increased in dorsal root ganglia (DRG) at 5 min after intradermal injection of capsaicin. p-PKB/Akt is distributed predominantly in small- and medium-sized DRG cells. After capsaicin injection, p-PKB/Akt (473) is colocalized with isotectin-B4 (IB4), tyrosine kinase A (TrkA), and calcitonin gene-related peptide (CGRP). Furthermore, most transient receptor potential vanilloid type 1 (TRPV1) positive DRG neurons double label for p-PKB/Akt. Behavioral experiments show that intradermal injection of a PI3K (upstream of PKB/Akt) inhibitor, wortmannin, dose-dependently inhibits the changes in exploratory behavior evoked by capsaicin injection. The PKB/Akt inhibitor, Akt inhibitor IV, has the same effect. The results suggest that the PKB/Akt signaling pathway in the periphery is activated by noxious stimulation and contributes to pain behavior.

Animals↗

Developmental neurotoxicity following premating maternal exposure to hexachlorobenzene in rats.

The maternal transfer of hexachlorobenzene (HCB) may place the developing organism at risk. The present study assessed the developmental neurotoxicity of HCB using a battery of behavioral tests. Two weeks prior to breeding, maternal rats were exposed via gavage to either 10 or 100 mg HCB/kg body weight. Behaviors evaluated in pups exposed maternally to HCB included the negative geotaxic reflex on postnatal day (PND) 6, 8, and 10, olfactory discrimination (PND 9-11), and the development of exploratory behavior (PND 15-20). Significant effects in these three tests indicated hyperactivity in HCB-exposed pups. No significant effects on learning (swim T-maze) or motor activity were detected in older offspring (PND 40 and 50 respectively). The acoustic startle response (ASR) revealed apparent age-related effects of maternal HCB exposure. On PND 23 pups from the high treatment group demonstrated significantly reduced ASR amplitude, whereas these same animals, tested on PND 90 (using a reflex modification design), showed elevated ASR amplitude relative to the controls. This work demonstrates that HCB is a behavioral teratogen, and suggests that human fetuses and suckling infants may be at risk from the neurotoxic effects of HCB.

Animals↗

The influence of a protein-methionine low diet on behavior of the rat offspring.

Spontaneous locomotor activity, exploratory behavior, pain reactivity and swimming ability were tested in 18-, 24-, 36-, and 60 days old pups from mothers which had been nourished on a protein-methionine low diet (PMLD) (7,8% protein, 0.1% of a daily requirement of methionine) for two months before conception throughout gestation and weaning; afterwards the young were fed on this diet until the age of 60 days and were compared with the offspring of rats, whose mothers and they themselves were nourished throughout hat period on a standard diet (STD). The motility of 24 and 36 days old pups receiving the PMLD was significantly higher and than of 60 days old lower than in controls. Analogous results were obtained in ambulation in the open field test. There were no differences in peeping and rearing in comparison with controls throughout the experiment, and only after 60 days both behavioral responses were significantly decreased. From the 24th day of life the PMLD rats revealed a statistically significant decrease in grooming and defecation frequency. There were no differences in swimming. The reactivity to a pain stimuli (hot-plate test) was higher than in controls on the 24th day of life. Generally, after an increase in activity on the first days of postnatal life a decrease in exploratory and emotional activity was observed after the 60th day of life.

Animals↗

Home bases formed to visual cues but not to self-movement (dead reckoning) cues in exploring hippocampectomized rats.

Spatial theory proposes that the hippocampus contributes to exploratory behavior allowing animals to acquire information about their environment. In the present study, the exploratory movements of control rats, bulbectomized (anosmic) rats and hippocampectomized rats using the neurotoxin N-methyl-D-aspartate (NMDA) were monitored on a large circular table without walls and around which visual cues were manipulated. The rats displayed organized spatial behavior in that they developed home bases, one or more places operationally defined as those in which they spent a preponderance of time, in which they moved slowly, and to which they returned after excursions. Control rats and hippocampectomized rats were similar in that they established home bases: (i) adjacent to a proximal stable or moving visual landmark; (ii) in relation to more distant visual room cues; and (iii) in relation to contextually conditioned visual cues. Nevertheless, in exploratory tests given under infrared light, a wavelength to which rats are insensitive, control rats and bulbectomized rats established one or more home bases that were not dependent upon surface (e.g. olfactory) cues, whereas home base behavior was absent/fragmented in hippocampectomized rats. Thus, exploratory behavior, as exemplified by home base behavior, is organized in control and hippocampectomized rats in relation to visual cues, but is not organized in hippocampectomized rats when visual cues are absent. This result is discussed in relation to the idea that the hippocampus contributes to spatial behavior that is dependent upon guidance (dead reckoning) derived from self-movement cues.

Analysis of Variance↗

Is a wild mammal kept and reared in captivity still a wild animal?

This study compared domestic guinea pigs (Cavia aperea f. porcellus; DGP) and two different populations of the wild cavy (Cavia aperea), its ancestor, to examine whether rearing of wild mammals in captivity affects their behavior and physiological stress responses. One population of wild cavies consisted of wild-trapped animals and their first laboratory-reared offspring (WGP-1). The animals of the other population were reared in captivity for about 30 generations (WGP-30). The spontaneous behavior of each of six groups of WGP-1 and WGP-30 and nine groups of DGP, each consisting of one adult male and two adult females, was analyzed quantitatively. Blood samples of the males were taken to determine cortisol, epinephrine, and norepinephrine concentrations. In addition, the exploratory behavior of 60-day-old male WGP-1, WGP-30, and DGP was investigated in an exploration apparatus. The domesticated animals displayed significantly less aggression, but significantly more sociopositive and male courtship behavior than their wild ancestors. In addition, DGP were much less attentive to their physical environment. Surprisingly, no behavioral difference was found between WGP-1 and WGP-30. Basal cortisol concentrations did not differ between wild and domestic guinea pigs. Catecholamine concentrations, however, as well as the challenge values of cortisol, were distinctly reduced in the DGP. WGP-1 and WGP-30 did not differ with respect to their endocrine stress responses. In the exploration apparatus both forms of wild cavies were much more explorative than the domestic animals. These data suggest that the long-term breeding and rearing of wild guinea pigs in captivity do not result in significant changes in behavior and hormonal stress responses. It appears to take much longer periods of time and artificial selection by humans to bring about characters of domestication in wild animals.

Aggression↗

Acute exposure to predator odor elicits a robust increase in corticosterone and a decrease in activity without altering proliferation in the adult rat hippocampus.

Stress has long been implicated as a major cause of depression in humans and more recently has been suggested to decrease neurogenesis, which may be a contributing factor to depression development. Animal models of stress may be a relevant tool for investigating links between neurogenesis and depression. This has largely been investigated using chronic stress models in rodents. However, stress may be chronic or experienced in discrete episodes. Acute stress may be particularly relevant to humans experiencing unexpected societal pressures and obligations. Our study examined the effect of acute stress on the proliferative phase of adult hippocampal neurogenesis. Young adult rats were exposed for 20 min to the predator odor TMT, a natural stressor for rodents with significant ethological relevance. BrdU IP injections were concurrent with TMT exposure to assess proliferation effects with animal sacrifice 2 h after BrdU injection. Robust stress responses were evident following TMT exposure as detected by elevated corticosterone (CORT) levels and a significant reduction in exploratory behavior. Exposure to TMT did not alter the number of BrdU-positive cells in the hippocampus despite physiological and behavioral evidence of stress. CORT level elevation has long been accepted as a marker of stress; however, this study indicates that increases in CORT level may not always correlate with diminished neurogenic proliferation. This study further suggests that various stressors may not operate through the same biological substrates resulting in a differential ability to modulate neurogenesis.

Animals↗

Between-subject transfer of emotional information evokes specific pattern of amygdala activation.

Emotional states displayed by an animal or a human can seriously affect behavior of their conspecifics. The amygdala plays a crucial role in the processing of emotions. In this study, we describe an experimental rat model of between-subject transfer of emotional information and its effects on activation of the amygdala. The rats were kept in pairs, and one animal (designated as "demonstrator") was treated to specific behavioral training of either foot-shock-reinforced context conditioning or just exposure to a novel context. We next examined the influence of the demonstrators on the exploratory behavior of their cagemates (called "observers") and the observers' performance of the acoustic startle response. We report that we can distinguish both groups of observers from the control animals (as shown by startle-response measure) and distinguish between observers (by means of indexing the exploration), with respect to whether they were paired with demonstrators treated to different experimental conditions. Furthermore, we show that the observers have most of their amygdala activated (as revealed by c-Fos mapping) to the same level as the demonstrators and, in the case of the central amygdala, to an even higher level. Moreover, the level of c-Fos expression in the observers reflected the specific behavioral treatment of the demonstrators with whom they were paired. Thus, in this study, we have shown that undefined emotional information transferred by a cohabitant rat can be evaluated and measured and that it evokes very strong and information-specific activation of the amygdala.

Amygdala↗

The genetic liability to stress and postweaning isolation have a competitive influence on behavioral organization in rats.

Rats housed in social isolation postweaning (isolates) show profound behavioral and neurobiological differences when compared to socially housed rats (socials). Fischer rats (F344) relative to Lewis rats are hyperresponsive and significantly more susceptible to stressful stimuli. This investigation tested the hypothesis that the behavioral effects of postweaning isolation are more pronounced in a strain of rats with high susceptibility to stress compared to a strain with low susceptibility to stress. Seventy male Sprague-Dawley, Lewis, and F344 rats were housed individually or in groups at weaning on Day 21 and tested on Day 85 in the Behavioral Pattern Monitor. There was no interaction between strain and postweaning isolation for measures of locomotor activity and exploratory behavior (holepoking). However, the postweaning isolation-induced increase in the frequency of repetitive straight movements, a measure of behavioral organization, was more pronounced in Lewis isolates compared to Sprague-Dawley and F344 isolates. These results do not support the hypothesis that rats with a higher susceptibility to stress show more pronounced changes in behavior following postweaning isolation; instead, increased susceptibility to stress may counteract the repetitive movement patterns induced by social isolation.

Animals↗

Social context affects how rhesus monkeys explore their environment.

This study reports on social modulation of exploratory behavior and response to novelty by members of a captive rhesus monkey colony. The group was trained to split in half, with one subgroup composed of dominant members only, the other of subordinates. The animals were then presented the same initially novel stimuli (i.e., sand-filled metal boxes containing hidden food items) in two social contexts differing in hierarchical composition. In a combined context, all group members (i.e., both subgroups together) were simultaneously presented the stimuli. In a split context, only members of the top or bottom half of the group (i.e., each subgroup in turn) was independently presented the stimuli. Subordinates responded similarly to dominant animals in the combined context but differently in the split context, where they were far more hesitant. Rank-related differences were evident in the way animals used their home compound and in their approach and responsiveness toward the stimuli. These findings show that social context influences how animals explore novel situations, possibly reflecting different social roles or status effects on the perception of social structure. Also, despite the complexity of primate social relationships, the separation technique produced no permanent or adverse effects on the social integrity of the group. This study shows that manipulating the social environment through separation training can be a powerful tool for assessing contextual influences on behavior.

Analysis of Variance↗

Crotoxin-induced behavioral effects in rats.

Crotoxin is the major component of Crotalus durissus terrificus venom. In view of the presence of high-affinity specific binding sites for crotoxin in the brain, the objective of this work was to investigate whether crotoxin induces behavioral effects in the open-field and hole-board tests. Adult male Wistar rats (180-220 g) treated with crotoxin, 100, 250 and 500 micrograms/kg, ip, administered 2 h before the test, presented statistically significant behavioral alterations (ANOVA for one-way classification complemented with Dunnet test, P < 0.05). In the open-field test, 250 and 500 micrograms/kg of crotoxin increased freezing (from 3.22 sec to 10.75 sec and 11.2 sec) and grooming (from 13.44 sec to 22.75 sec and 21.22 sec) and decreased ambulation (from 64.8 to 39.38 and 45.8). The dose of 500 micrograms/kg also decreased rearing (from 24.9 to 17.5). In the hole-board test, 500 micrograms/kg of crotoxin decreased head-dip count (from 6.33 to 4.00). All the crotoxin-induced behavioral effects were antagonized by an anxiolytic dose of diazepam (1.5 mg/kg, ip. 30 min before the tests). These results show that crotoxin reduced open-field activity and exploratory behavior as well. We suggest that these effects express an increased emotional state induced by this toxin.

Analysis of Variance↗

Effects of fencamfamine withdrawal in rats.

1. The effects produced by discontinuation of long-term treatment with fencamfamine (FCF) were evaluated recording behavioral and body weight changes. 2. 48 hr after withdrawal of FCF rats showed a significant decrease in exploratory behavior when compared to saline-treated ones. 3. Discontinuation of treatment with FCF resulted in a significant increase in body weight on days of drug withdrawal. 4. These results suggest that FCF caused signs of withdrawal similar to other psychostimulant drugs.

Animals↗

Statistics of decision making in the leech.

Animals continuously decide among different behaviors, but, even in invertebrates, the mechanisms underlying choice and decision are unknown. In this article, leech spontaneous behavior was tracked and quantified for up to 12 h. We obtained a statistical characterization, in space and time domains, of the decision processes underlying selection of behavior in the leech. We found that the spatial distribution of leech position in a uniform environment is isotropic (the same in all directions), but this isotropy is broken in the presence of localized external stimuli. In the time domain, transitions among behaviors can be described by a Markov process, the structure of which (allowed states and transitions) is highly conserved across individuals. Finally, a wide range of recurrent, deterministic motifs was identified in the apparently irregular and unstructured exploratory behavior. These results provide a rigorous description of the inner dynamics that control the spontaneous and continuous flow of behavioral decisions in the leech.

Animals↗

The effect of dose, novelty, and exploration on amphetamine-produced stereotyped behavior.

Four experiments are presented. The first experiment demonstrated that the incidence of steretyped behavior was a monotonic increasing function of amphetamine dose. Variations in the form of the response to dose are described. The next two studies examined the relationship between environmental novelty and amphetamine-produced stereotypy. This behavior was observed less among subjects placed into novel environments than among subjects placed into familiar environments. The ability of novel stimuli to evoke exploratory responses incompatible with stereotypy was suggested as the basis for this effect. This interpretation was supported in a final experiment, which observed exploratory behavior and general activity, as well as amphetamine-produced stereotypy in subjects exposed to a novel stimulus in an otherwise familiar environment. All four experiments were interpreted as supporting a unified conception of amphetamine-produced and pathological sterotyped behaviors.

Animals↗

[Anxiety and behavior in WAG/Rij strain rats with genetically induced absence attacks].

Behavior of nonlinear rats and animals from Wistar and WAG/Rij (with inborn generalized absence epilepsy) strains was examined in the elevated plus-maze and the hole board. WAG/Rij rats demonstrated low exploratory behavior in both tests. In the elevated plus-maze, WAG/Rij rats were more balanced and more anxious than Wistar and nonlinear rats. Administration of ethosuximide completely eliminated spike-wave discharges but did not change behavioral interstrain differences. Since the spike-wave patterns develop in WAG/Rij at the age of 3 months, the behavior of young (2-moth-old) pups from different strains was compared and significant differences were revealed. Correlation between the genetically defined features (spike-wave discharges) and behavioral peculiarities in WAG/Rij rats is supposed.

Aging↗

Serotonin 2C receptors within the basolateral amygdala induce acute fear-like responses in an open-field environment.

Several studies indicate a role for the serotonin 2 subfamily (5-HT(2A), 5-HT(2B), 5-HT(2C)) in mediation of fear and anxiety responses. The current study began to examine the effects of stimulating 5-HT(2C) receptors within the basolateral (BLA) or central nucleus of the amygdala (CeA) on acute fear-like responses in rats. Bilateral intra-BLA infusions of mCPP (3-3000 pmol), a mixed 5-HT(2) agonist, produced ultrasonic vocalization and reduced exploratory behavior while increasing the latency to investigate a novel object. These responses were attenuated by SB-242084, a 5-HT(2C)-specific antagonist. Furthermore, a selective 5-HT(2C) agonist, IL-639, produced a similar repertoire of behavioral effects with the exception of effects on time spent in the center of an open-field arena. Finally, infusions of mCPP into the CeA produced no anxiogenic behaviors suggesting that 5-HT(2C) receptors primarily within the BLA are responsible for many of the acute fear-like responses reported here. To characterize further the neural circuits associated with 5-HT(2C)-mediated fear responses, we assessed c-fos mRNA expression after intra-BLA infusions of mCPP, IL-639 or their vehicles. Whereas the overall regional pattern of c-fos mRNA induction for the two compounds was distinct, c-fos activation was confined primarily to limbic nuclei with the medial prefrontal cortex as a common regional target of each drug. These results suggest that activation of 5-HT(2C) receptors within the BLA influences the activity of limbic circuits involved in the expression of acute innate fear responses.

Aminopyridines↗