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D Caroline Blanchard

Publications and source records attributed to D Caroline Blanchard.

At least 19 recordsLinked to original sources
PubMed2006

Effects of D-amphetamine on defensive behaviors related to fear and anxiety.

In rodents, the administration of amphetamine has been associated with increased locomotor activity and stereotypy, and an emerging body of evidence suggests that it also enhances anxiety-like behavior in a number of animal models. Ethoexperimental analyses have outlined an array of defensive behaviors to threat that are responsive to anxiolytic, panicolytic-like and panicogenic agents, suggesting that the characterization of amphetamine effects on defense may provide further insights into the emotionality consequences of this drug. In Experiment 1, intraperitoneal administration of amphetamine (1 and 5 mg/kg, i.p.) on defensive behavior elicited by a predatory threat stimulus was assessed via time sampling analysis. Amphetamine dose-dependently suppressed freezing while potentiating locomotor activity. In Experiment 2, amphetamine was administered intravenously and animals were tested in a Rat Runway Test (RRT), designed to individually elicit a variety of defensive behaviors to a conspecific threat. All three doses of amphetamine (1, 2 and 5 mg/kg) produced robust changes in defensive responding by increasing directional flight behavior, jump escapes and upright/orientations. The results are in agreement with those of another psychostimulant, cocaine, and support a previously hypothesized link between flight and panic.

Animals↗
PubMed2006

Central infusion of ovine CRF (oCRF) potentiates defensive behaviors in CD-1 mice in the Mouse Defense Test Battery (MDTB).

Following intracerebroventricular (i.c.v.) injection of ovine CRF (oCRF), an endogenous peptide agonist at both CRF1 and CRF2 receptors, defensive behaviors of CD-1 mice were evaluated in the Mouse Defensive Test Battery (MDTB). Behavioral measures taken before, during, and after predator (a hand-held anesthetized rat) confrontation included exploratory activity, risk assessment, avoidance, flight, freezing, defensive threat/attack, and residual emotional responses. Both low (0.1 nmol) and high (0.2 nmol) doses of oCRF robustly suppressed exploratory activities and increased risk assessment during the initial familiarization period. Flight speed and jump escapes when the mouse was chased were significantly elevated by the 0.2 nmol dose. Both doses enhanced freezing and avoidance to a distant predator when the escape route was blocked. The 0.2 nmol dose also potentiated flight responses to a contacting predator in a highly confined space. Both oCRF groups traveled shorter distances and exhibited less escape attempts following the removal of the threat stimulus. These findings indicate that non-selective activation of corticotropin-releasing factor (CRF) receptors via ventricular infusion of oCRF potentiates defensive behaviors relevant to the demand of specific challenges, generally enhancing the predominant defensive behavior in each specific situation.

Analysis of Variance↗
PubMed2006

Effects of lesions to the dorsal and ventral hippocampus on defensive behaviors in rats.

This study investigated the role of the hippocampus in both unconditioned and conditioned defensive behaviors by examining the effects of pretraining ibotenic acid lesions to the dorsal and ventral hippocampus in male Long-Evans hooded rats exposed to three types of threat stimuli: cat-odor, a live cat and footshock. Defensive behaviors were assessed during exposure to cat-odor and a live cat, and immediately following the presentation of footshock. Conditioned defensive behaviors were also assessed in each context 24 h after initial threat exposure. During both unconditioned and conditioned trials, dorsal hippocampal lesions failed to significantly alter any behavioral measure in each test of defense. In contrast, ventral hippocampal lesions significantly reduced unconditioned defensive behaviors during exposure to cat-odor without producing any observable effects during cat exposure. Furthermore, ventral lesions significantly attenuated conditioned defensive behaviors following the administration of footshock and during re-exposure to each context. These results suggest a specific role for the ventral, not dorsal, hippocampus in modulating anxiety-like behaviors in certain animal models of defense.

Aggression↗
PubMed2005

Lesions of structures showing FOS expression to cat presentation: effects on responsivity to a Cat, Cat odor, and nonpredator threat.

Exposure of rats to a cat elicits Fos activity in a number of brain areas or structures. Based on hodological relationships of these, Canteras has proposed a medial hypothalamic defense system, with input from several forebrain sites. Both electrolytic and neurotoxic lesions of the dorsal premammillary nucleus, which shows the strongest Fos response to cat exposure, produce striking decrements in a number of defensive behaviors to a cat or to cat odor stimuli, but do not have a major effect on either postshock freezing, or responsivity to the odor of a female in estrus. Neurotoxic lesions of the medial amygdala produce decrements in defensiveness to predator stimuli, particularly odor stimuli, that are consistent with a view of this structure as involved with allomonal cues. While dorsal hippocampal lesions had little effect on responsivity to predator stimuli, neurotoxic lesions of the ventral hippocampus reduced freezing and enhanced a variety of nondefensive behaviors to both cat odor and footshock, with similar reductions in defensiveness during context conditioning tests for cat odor, cat exposure and footshock. These results support the view that the dorsal premammillary nucleus is strongly and selectively involved in control of responsivity to predator stimuli. Structures with important input into the medial hypothalamic defense system appear also to be functionally involved with antipredator defensive behaviors, and these lesion studies may suggest specific hypotheses as to the particular defense functions of different areas.

Animals↗
PubMed2005

Some suggestions for revitalizing aggression research.

Aggression research is moribund. Lack of research over the past two decades has left many issues. (1) Understanding varieties of agonistic behaviour in an ethological context: categories differing in behaviours, target sites and function include offence, defensive attack, and predation. Biological systems must be determined for each of these. (2) Insuring availability of ethologically valid laboratory models of agonistic behaviour and describing (possibly species-specific) standards for these. We shall present models and consider the problematic issue of biting. (3) Use of non-damaging behavioural markers that precede fights. These should be independently analysed, measured and verified as potential substitutes for biting attack. (4) Interaction between fear and offensive aggressive motivation systems must be understood in order to evaluate whether independent variable (e.g. pharmacological, genetic) effects involve a specific motivational system rather than reflecting changes in oppositional systems. (5) Knowledge of agonistic systems and their biological basis must be extended to humans, focusing on both normal aggression in each category, and the development of models of aggressive psychopathology. Placing aggression research in an ethological context and focusing on its biomedical relevance may help to counter forces suppressing this work.

Aggression↗
PubMed2004

AVP V1b selective antagonist SSR149415 blocks aggressive behaviors in hamsters.

Arginine vasopressin (AVP) has been implicated in a variety of physiological and behavioral responses to stress. Synthesis of receptor-selective AVP agonist and antagonist compounds allows differential analysis of the specific roles of particular receptor subtypes with respect to these responses. Here, effects of the recently synthesized AVP V1b selective antagonist, SSR149415, were examined for offensive aggression in male Syrian hamsters, using a resident-intruder paradigm. Oral administration of vehicle or 1, 10, or 30 mg/kg of SSR149415 to resident hamsters was followed by evaluation of a range of aggression-related measures of residents confronted by intruders. The 10 and 30 mg/kg doses significantly reduced the duration of offensive sideways and chase behaviors, and the 30 mg/kg dose also reduced chase frequency. The 10 and 30 mg/kg dose also significantly reduced frequency and duration of olfactory investigation and duration of flank marking. These findings suggest a link between activity of the V1b receptor and the modulation of offensive aggression. These findings agree with previous research on V1b receptor effects in suggesting that antagonism of this receptor may be useful in modulating a range of emotional responses to highly stressful or threatening conditions.

Aggression↗
PubMed2004

Modulation of predatory odor processing following lesions to the dorsal premammillary nucleus.

Previous studies have shown that electrolytic lesions of the dorsal premammillary nucleus (PMd) produce robust reductions in responsivity of rats to the presence of a live predator as well as to its odor, suggesting a critical role for the PMd in the modulation of defense. The present study investigated whether disruptions in defensive responding were specific to predators or if they may indicate a more general deficit in responding to pheromonal odors. Sexually naive male rats with bilateral ibotenic acid lesions of the PMd were exposed to the odor of a female rat in estrus as well as to the presence of cat odor, and, a live cat. PMd lesions produced a dramatic reduction in freezing and avoidance to the cat odor; and, reductions in freezing, enhanced activity and risk assessment to cat exposure. However, PMd lesions produced no changes in response to the presentation of the female odorant. These results confirm earlier findings of attenuation in defensiveness following electrolytic PMd lesions while extending these findings to suggest that the reduced defensiveness occurs specifically in response to predatory odors.

Animals↗
PubMed2004

Effects of the CRF1 antagonist SSR125543A on aggressive behaviors in hamsters.

Corticotropin-releasing factor (CRF) and its receptor subtypes have been implicated in endocrine and behavioral responsivity to stress and emotion, including fear, anxiety, and aggression. SSR125543A is a new nonpeptide selective antagonist at the CRF1 receptor that has been shown to produce an anxiolytic-like effect in a number of animal models of anxiety. The present study investigated effects of an oral dose of 10, or 30 mg/kg of SSR125543A on aggressive behaviors of resident male Syrian hamsters toward male intruders. The high dose (30 mg/kg) of the CRF1 receptor antagonist produced a higher latency to bite and lower lateral attack frequencies and chase durations, indicating a reduction in aggression toward intruders in resident hamsters. The same dose of SSR125543A also enhanced frequency and duration of olfactory investigation, indicating that neither avoidance of the opponent nor deficiency in social activity is responsible for the reduction in aggression seen in these animals.

Aggression↗
PubMed2004

The rat exposure test: a model of mouse defensive behaviors.

In order to facilitate behavioral, and potentially pharmacological, analyses of risk assessment behaviors in mice, a rat exposure test (RET) was devised and evaluated. This test provides a home chamber connected via a tunnel to a rat (predator) exposure area. Familiar substrate is provided to permit burying, and mouse subjects are habituated to the apparatus prior to exposure to an amphetamine-activated rat. In comparison to toy-rat-exposed controls, rat-exposed BALB/c mice showed significantly more risk assessment [stretch attend posture (SAP) and stretch approach], freezing, and avoidance (time in the home chamber), and less time in contact with the wire mesh screen between itself and the threat stimulus. When BALB/c, C57BL/6, CD-1, and Swiss-Webster mice were compared in this test, the two inbred strains (BALB/c and C57BL/6) tended to show more extreme values of particular defensive behaviors, compared to the two outbred strains (Swiss-Webster and CD-1). C57BL/6 mice showed more avoidance and higher levels of SAP, freezing, and burying than BALB/c and more than one or both outbred strains as well. BALB/c mice showed little defensive burying, both in comparison to toy-exposed controls (Experiment 1), and in comparison to the three other strains in Experiment 2. These findings are somewhat at variance with characterizations of anxiety in C57BL/6 and BALB/c mice, based on tests utilizing novel areas and noxious stimuli, suggesting strain differences in defensiveness to such stimuli, compared to antipredator defense levels. Nonetheless, with the exception of burying in BALB/c mice, all strains showed all defensive behaviors measured to the rat stimulus. In particular, SAP levels were substantial in all strains tested, suggesting the usefulness of this test in assessment of the role of risk assessment in defense.

Aggression↗
PubMed2003

Dorsal premammillary nucleus differentially modulates defensive behaviors induced by different threat stimuli in rats.

Lesions of the dorsal premammillary nucleus (PMd) have been reported to produce dramatic reductions in responsivity of rats to a live cat. Such lesions provide a means of analyzing the potentially differential neural systems involved in different defensive behaviors, and the relationship between these systems and concepts such as anxiety. Rats with bilateral electrolytic lesions of the PMd were run in an elevated plus maze (EPM), exposed first to cat odor and then to a live cat, and assessed for postshock freezing and locomotion. PMd lesions produced a dramatic reduction in freezing, avoidance, and stretch attend to the cat odor stimulus, and reduction in freezing, with greater activity, and enhanced stretch approach to cat exposure. However, PMd lesions had minimal effects in the EPM, and postshock freezing scores were unchanged. These results confirm earlier findings of reduced defensiveness of PMd-lesioned rats to a cat, extending the pattern of reduced defensiveness to cat odor stimuli as well, but also suggest that such lesions have few effects on nonolfactory threat stimuli.

Aggression↗
PubMed2003

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic.

The Mouse Defense Test Battery was developed from tests of defensive behaviors in rats, reflecting earlier studies of both acute and chronic responses of laboratory and wild rodents to threatening stimuli and situations. It measures flight, freezing, defensive threat and attack, and risk assessment in response to an unconditioned predator stimulus, as well as pretest activity and postthreat (conditioned) defensiveness to the test context. Factor analyses of these indicate four factors relating to cognitive and emotional aspects of defense, flight, and defensiveness to the test context. In the Mouse Defense Test Battery, GABA(A)-benzodiazepine anxiolytics produce consistent reductions in defensive threat/attack and risk assessment, while panicolytic and panicogenic drugs selectively reduce and enhance, respectively, flight. Effects of GABA(A)-benzodiazepine, serotonin, and neuropeptide ligands in the Mouse Defense Test Battery are reviewed. This review suggests that the Mouse Defense Test Battery is a sensitive and appropriate tool for preclinical evaluation of drugs potentially effective against defense-related disorders such as anxiety and panic.

Animals↗
PubMed2003

Conditioning and residual emotionality effects of predator stimuli: some reflections on stress and emotion.

The advantages of using predator-related odor stimuli to study emotional responses in laboratory tests depend on whether such stimuli do elicit a relatively complete pattern of emotionality. This has been confirmed for cat fur/skin odor stimuli, which elicit a range of defensive behaviors in rats that may be reduced by anxiolytic drugs, produce residual anxiety-like behavior in the elevated plus maze and support rapid aversive conditioning to the context in which they were encountered. Although the synthetic fox fecal odor, trimethylthiazoline (TMT), elicits avoidance similar to that seen in response to cat fur/skin odor, this avoidance does not respond to anxiolytic drugs. In addition, TMT does not produce residual anxiety-like behaviors in the elevated plus maze, nor does it support conditioning. As natural cat feces also elicit avoidance but fail to support conditioning, it is possible that the ability of a predator-related odor to serve as an effective unconditioned stimulus (US) relates to its predictive status with reference to the actual presence of the predator. Avoidance per se may reflect that a stimulus is aversive but not necessarily capable of eliciting an emotional response. This view is consonant with findings in a Mouse Defense Test Battery (MDTB) measuring a wide range of defensive responses to predator exposure. A contextual defense measure that may reflect either conditioned or residual but unconditioned emotional responses was almost never reduced by drug effects unless these also reduced risk assessment or defensive threat/attack measures. However, reductions in contextual defense without changes in flight/avoidance measures were much more common. These findings suggest that flight/avoidance, although it obviously may occur as one component of a full pattern of defensive and emotional behaviors, is also somewhat separable from the others. When-as appears to be the case with TMT-it is the major or perhaps only consistent defensive behavior elicited, this may reflect a stimulus that is aversive or noxious but with little ability to predict the presence of threat or danger. That such stimuli fail to support rapid aversive conditioning suggests the need for a reanalysis of the characteristics required for an effective aversive US.

Animals↗
PubMed2003

Problems in the study of rodent aggression.

Laboratory research has produced detailed descriptions of aggression and defense patterns in the rat, mouse, and hamster, showing strong similarities, but also some differences, across these species. Research on target sites for attack, in conjunction with analyses of the situational antecedents of attack behaviors and of responsivity of these to conditions that elicit fear, has also provided a strong basis for analysis of offensive and defensive aggression strategies and for identification of combinations of these modalities such as may occur in maternal aggression. These patterns have been empirically differentiated from phenomena such as play fighting or predation and compared for laboratory rodents and their wild ancestors. An array of tasks, suitable for use with pharmacological and experimental manipulations, is available for analysis of both aggression and defense. These developments should produce a firm basis for research using animal models to analyze a broad array of aggression-related phenomena, including systematic approaches to understanding the normal antecedents and consequences of each of several differentiable types of aggressive behavior. Despite this strong empirical and analytic background, laboratory animal aggression research has been in a period of decline, spanning several decades, relative to comparable research focusing on areas such as sexual behavior or stress. Problems that may have contributed to the relative neglect of aggression research include confusion about the interpretation of different tasks for eliciting aggression; difficulties and labor intensiveness of observational measures needed for an adequate differentiation of offensive and defensive behaviors; analytic difficulties stemming from the sensitivity of offensive aggression to the inhibitory effects of fear or defensiveness; lack of a clear relationship between categories of aggressive behavior as defined in animal studies and those used in human aggression research; and the social and political difficulties undermining support for research on a topic that, when applied to humans, provides a stigmatizing label. While all of these provide some rationale for eschewing aggression research, aggression remains a serious social, economic, health, and political problem. The neglect of research in this area contributes to an ongoing failure to understand the degree of similarity across mammalian species in the antecedents, neural systems, behavioral expression, and outcomes of aggression. This failure, in turn, hinders analyses of normal and abnormal forms of aggression and of the appropriate roles of the former in society, reducing the possibility of sensitive and effective approaches to control inappropriate human aggressive behaviors.

Aggression↗
PubMed2003

What can animal aggression research tell us about human aggression?

Research on endocrinological correlates of aggression in laboratory animals is implicitly motivated by an expectation that the results of such studies may be applicable to human aggression as well. Research with a focus on the stimulus antecedents of aggression, its response characteristics, and its outcomes suggests a number of detailed correspondences between offensive aggression in laboratory rodents and human angry aggression. These include resource (including status and territory) competition as motives that are particularly elicited by conspecific challenge situations and, when the aggression is successful, outcomes of reduction of challenge and enhancement of resource control and status. Although the response characteristics of human aggression have been dramatically altered by human verbal, technological, and social advancements, there is some evidence for targeting of blows, similar to a well-established pattern for offensive aggression in many nonhuman mammals. Finally, for people as well as for nonhuman mammals, fear of defeat or punishment is a major factor inhibiting the expression of offensive aggression. While defensive aggression has been very little researched in people, it may represent a different phenomenon than angry aggression, again providing a parallel to the offense-defense distinction of laboratory rodent studies.

Aggression↗
PubMed2003

Bringing natural behaviors into the laboratory: a tribute to Paul MacLean.

Paul MacLean's work has exemplified and encouraged an approach in which natural behaviors are elicited and investigated in laboratory settings. Our own experiences with bringing natural behaviors into the laboratory indicate that this is best achieved by providing the social and environmental stimuli necessary to support these behaviors and by an initial process of ethological/observational analysis of them. Examples discussed in support of these suggestions include the development of more natural habitats, including visible burrow systems (VBS), for fossorial rodents such as rats and mice; analysis of aggressive and defensive behaviors among social groups in such habitats and to introduced predators; and the development of defense test batteries in which individual defensive behaviors may be elicited through manipulations of threat and environmental stimuli. These situations have proved useful in analysis of the effects of drugs active against anxiety-related psychopathologies. However, an equally important use for them is in the analysis of normal defensive and aggressive behaviors. Detailed analysis of natural behaviors in socially and environmentally adequate situations provides an important link between molecular findings and both normal and pathological behavior patterns. Investigation of natural behaviors in adequate stimulus contexts does not represent an antiexperimental stance but one that supplements and enhances the generalizability of more conventional experimental laboratory approaches.

Adaptation, Physiological↗
PubMed2003

Infralimbic D2 receptor influences on anxiety-like behavior and active memory/attention in CD-1 mice.

Ventromedial prefrontal cortical (vmPFC) dopamine (DA) influences attentional aspects of cognition and anxiety-like behavioral responding in rodents. The present study investigated the role of D2 receptors on spontaneous alternation in the Y-maze and anxiety-like behavior in a two-trial elevated plus-maze (EPM) procedure in CD-1 mice following vmPFC infusions of the D2 antagonist, sulpiride, and the D2 agonist, quinpirole. Pretrial 1 quinpirole infusions did not influence any anxiety measure (with the exception that the lowest dose increased protected stretch attends), but reduced protected exploration activity (closed-arm entry/time ratios and wall rearing). In Trial 2 24 h later (no injection), quinpirole exerted an anxiolytic behavioral profile relative to Trial 2 control mice (enhanced open-arm entry/time ratios, unprotected head dips), with no effects on protected exploration or risk assessment activity. Pretrial 1 sulpiride infusions enhanced unprotected exploration (open-arm entry/time ratios, unprotected stretch attend, and head dips), but did not influence protected exploration or risk assessment in the EPM. In Trial 2, 24 h later (no injection), sulpiride extended this anxiolytic profile to reduced protected exploration and risk assessment activity (closed-time ratio, protected stretch attend, and head dips). In the Y-maze, whereas quinpirole disrupted alternation performance (5- and 10-nmol dose) concomitant with marked repetitive same-arm returns (SAR) at the highest dose, sulpiride disrupted alternation performance concomitant with marked repetitive SAR behavior at the lowest dose only. These data indicate that although infralimbic (IL) quinpirole and sulpiride infusions similarly disrupted alternation performance in the Y-maze and reduced Trial 2 anxiety-like responding in the EPM, these drugs differentially produced these effects.

Animals↗
PubMed2003

Failure to produce conditioning with low-dose trimethylthiazoline or cat feces as unconditioned stimuli.

Trimethylthiazoline (TMT), a derivative of fox feces, has been reported to fail to produce aversive conditioning as an unconditioned stimulus (UCS) when presented in large amounts (I. S. McGregor, L. Schrama, P. Ambermoon, & R. A. Dielenberg, 2002). Experiment I evaluated very low TMT levels that nonetheless produced defensive behaviors in rats during exposure. Although each level (0.01, 0.05, and 0.10 microl TMT) produced significant change in defensiveness, none resulted in significant changes the following day in the absence of TMT. Experiment 2 evaluated cat urine, cat feces, and cat fur/skin odor against a no-odor control. Urine produced no significant changes, but feces and fur/skin odors elicited virtually identical changes in defensive behaviors during exposure. When tested the next day in the absence of odor, the fur/skin odor-exposed group showed significant differences on the same behaviors as during exposure, but the feces-exposed group showed no differences on any measure. Results suggest that lack of conditioning to TMT may relate to the type of predator odor rather than the amount, predator species, or possible lack of odor components in TMT that are present in natural feces. Predator feces may also be less effective as a UCS because they are poorly predictive of the actual presence of the predator, suggesting the need for a reevaluation of UCS functions in aversive conditioning.

Animals↗