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Biomedical subjects

D C Blanchard

Publications and source records attributed to D C Blanchard.

At least 19 recordsLinked to original sources

Evidence for differential effects of 8-OH-DPAT on male and female rats in the Anxiety/Defense Test Battery.

The Proxemics/Activity test and the Eat/Drink test, two components of the Anxiety/Defense Test Battery, were developed to measure defensive reactions to situations associated with a natural predator (cat). In the present studies the behavioral effects of 8-OH-DPAT treatment (0.01-1.0 mg/kg, SC) were entirely consistent with anxiety/fear reduction. These effects included an increase in time spent near the cat compartment, and a complimentary decrease in time spent farthest from this compartment, together with an increase in transits and locomote behavior. 8-OH-DPAT (1.0 mg/kg) also increased eat frequencies and durations (highly preferred food) both during and following cat presentation, without influencing drinking. This finding is discussed with reference to previous findings with 8-OH-DPAT in studies assessing both food intake and anxiolysis. Interestingly, 8-OH-DPAT was more potent in a majority of its effects in female subjects, a finding consistent with recent neurochemical data. These findings provide important behavioral evidence for a sexual differentiation in 5-HT function, and support the case for greater emphasis on female subjects in animal models of anxiety.

8-Hydroxy-2-(di-n-propylamino)tetralin

MK-801 produces a reduction in anxiety-related antipredator defensiveness in male and female rats and a gender-dependent increase in locomotor behavior.

The present study investigated the effects of the non-competitive NMDA antagonist MK-801 (0.04-0.16 mg/kg), on antipredator defensive reactions of male and female rats in three paradigms comprising the Anxiety/Defense Test Battery (A/DTB). In order to facilitate interpretation of data from the above study, the behavioral effects of the compound were also assessed in the non-threatening environment of the home cage. The data indicate a marked gender difference in the locomotor effects of the compound with females, but not males, showing a dose-dependent increase in general locomotor activity, a decrease in freezing, and a loss of balance at the highest dose, in both non-threatening and threatening contexts. The behavioral profile for males in the A/DTB included decreased orientation to and proxemic avoidance of the cat stimulus or stimulus site, and increased transits and eating in the cat situation. Contacts with the cat odor stimulus were increased, as was normal, curved back, locomotion in this test. In the absence of non-specific locomotor effects for males, this profile for the A/DTB provides convincing evidence for anxiety/fear reduction with MK-801. While locomotor effects tended to mask the putative anxiolytic properties of the compound in females, evidence remains from behavioral changes not attributable to a locomotor influence to indicate anxiety/fear reduction in this sex.

Aggression

The anxiety/defense test battery: influence of gender and ritanserin treatment on antipredator defensive behavior.

The anxiety/defense test battery has been developed to measure defensive reactions in laboratory rats to both direct exposure to, and stimuli associated with, a natural predator, the domestic cat. The present investigation confirmed earlier findings with each test providing a distinct behavioral profile following exposure to predator stimuli. In addition, the data showed a consistent gender difference in a number of these behavioral measures, indicating that females are more defensive than males. These effects included reliability higher levels of cat avoidance and crouching, with lower levels of transits, lying and drinking for cat-exposed females. Similarly, females exposed to a cat odor stimulus showed a reliably higher level of stretch attend and flat back approach behaviors (risk assessment) towards the stimulus block. The 5-HT2 antagonist, ritanserin, failed to provide significant indication of anxiolytic activity, and had minimal influence on antipredator defensive behavior. An important exception to this profile was a reliable decrease in stretch attend behavior to a cat odor stimulus in females but not males. Overall, these findings suggest a complex relationship between gender, antipredator defensive behavior, and anxiolytic drug treatment.

Animals

Morphine attenuates antipredator ultrasonic vocalizations in mixed-sex rat colonies.

Mixed-sex groups of laboratory rats living in a visible burrow system (VBS) emit 18-27 kHz ultrasound and retreat to the burrow when a cat is placed in the open area of the VBS. The total duration of ultrasonic vocalizations was reliably reduced by pretreatment with 5 mg/kg morphine. In a subsequent study using male-female colony pairs, presentation of a cat to individual rats in the absence of their colony mate indicated significant gender differences in base frequency, degree of emission, and characteristics of pulses elicited. Specifically, females showed a greater number and duration of vocalizations, of higher frequency (kHz), and with shorter individual pulse durations than males. In the same study, morphine (5 mg/kg) produced a general decrease in the level of ultrasonic emissions in both sexes, reduced the mean base frequency (kHz), and increased the mean duration of individual pulses. These data suggest that endogenous opioid mechanisms may be involved in the mediation of ultrasonic vocalization in response to a predator, and are discussed with reference to known involvement of such systems in defensive responding.

Animals

Domestication alters 5-HT1A receptor binding in rat brain.

Serotonin-1A receptor binding density was compared in the brains of wild and domesticated adult male Rattus norvegicus using in vitro receptor autoradiography of [3H]8-hydroxy-2-[n-dipropylamino]tetraline (DPAT). While both groups exhibited similar patterns of labeling, [3H]DPAT binding density was significantly (p less than or equal to 0.05) lower in the median raphe nucleus and greater in superficial entorhinal cortex and rostral dentate gyrus of domesticated compared to wild rats. The results suggest that specific serotonergic circuits from the median raphe nucleus to the entorhinal and hippocampal regions might be involved in regulation of the defensive behaviors that differ profoundly between wild and domesticated rats. The relationship of these putative differences to behavioral disorders such as anxiety and depression in humans is discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin

Sex differences in the incidence and sonographic characteristics of antipredator ultrasonic cries in the laboratory rat (Rattus norvegicus).

Long-Evans rats (Rattus norvegicus; ns = 10 males and 10 females) in a burrow system responded to a cat in the open area by retreating to a burrow and emitting ultrasounds of 18-27 kHz. Females made more frequent ultrasonic cries, with longer durations of ultrasounds. In a 2nd study (ns = 19 males and 19 females), sonographic analyses confirmed the more frequent vocalizations of females and indicated that the sound pulses of females were reliably shorter in duration and of higher base frequency than those of males. Also, females emitted more pulses per pulse train with shorter within-train interpulse intervals. Six basic pulse forms were determined, and males emitted more (70%) pulses with negatively accelerated descending frequencies than females (25%). The findings indicate that female rats show qualitatively different antipredator vocalizations than do males and add to previous findings of higher levels of female antipredator defensiveness.

Animals

Serotonin, but not dopamine, metabolites are increased in selected brain regions of subordinate male rats in a colony environment.

Subordinate male laboratory rats maintained in mixed-sex groups in a Visible Burrow System habitat show a complex pattern of stress-related changes including enhanced defensive behavior, early mortality and increased voluntary ethanol consumption. Analysis of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels indicated that 5-HT levels do not differ between colony subordinates, colony dominants, and singly-housed control animals. However, 5-HIAA levels were higher in subordinates than either dominants or control animals in the preoptic area, amygdala, hippocampus, and spinal cord, and, were higher than dominants only, in entorhinal cortex. Subordinates' regional 5-HIAA/5-HT ratios were reliably higher than those of dominant or control animals in midbrain and spinal cord and reliably higher than dominants only, in hypothalamus. Dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels and DA/DOPAC ratios were affected neither in hypothalamus nor midbrain. These findings suggest that a consistent increase of 5-HIAA levels in selected brain regions of subordinate rats may represent a biological substrate for a well-characterized pattern of alterations in defensive behaviors for these animals.

Animals

Twenty-two kHz alarm cries to presentation of a predator, by laboratory rats living in visible burrow systems.

When a cat was presented to groups of 3 male and 2 female laboratory rats in the open area of a visible burrow system, the rats retreated to the burrow system and showed high levels of 18-24 kHz ultrasonic cries during the cat presentation and for 30 min following removal of the cat. Latency to make ultrasonic vocalizations, durations of these vocalizations, and duration in the burrow systems were all strikingly and reliably different during and after cat exposure in comparison to similar periods with a control (stuffed cat toy) stimulus. However, when individual rats were exposed to a cat in an open area of similar size, ultrasonic cry production was minimal. Also rats exposed individually to a cat in an apparatus providing an escape chamber similarly showed no ultrasonic cries, indicating that concealment per se is not a sufficient condition for their appearance. These results suggest that the production of ultrasonic vocalizations during and after exposure to a predator is greatly facilitated by the presence of familiar conspecifics, and may serve as alarm cries. While the alarm cry hypothesis also suggests a possible function for 18-24 kHz ultrasounds in the context of copulation and intraspecies aggression, the sonographic and functional relationships among the cries emitted in these different situations remain to be analyzed.

Animals

"Paradoxical" effects of morphine on antipredator defense reactions in wild and laboratory rats.

In a Fear/Defense Test Battery, measuring defensive reactions to a present, approaching and contacting predator, the highest dose of morphine tested (7.5 mg/kg) reliably reduced vocalization to dorsal contact, to vibrissae stimulation, and to an anesthetized conspecific in laboratory-bred wild R. norvegicus. Except for a dose-dependent reduction in flinch/jump reactions to dorsal contact (taps), other defensive behaviors (flight, freezing, etc.) were not reliably altered by morphine treatment (0, 1.0, 2.5, 7.5 mg/kg). Vocalization responses to vibrissae stimulation in wild-trapped R. rattus were reliably increased following naloxone (1.0 and 10.0 mg/kg) administration, lending support for opiate receptor involvement in the mediation of defensive vocalization. In the Anxiety/Defense Test Battery, measuring defensive reactions to situations associated with a predator (cat) or with cat odor, laboratory rats showed no decrease in defensive behavior with morphine (0, 1.0, 5.0 mg/kg). In direct contrast to the above findings, the effects of morphine treatment in this test battery suggested a generalized increase in defensiveness to noncontacting and nonpainful threat stimuli. These effects included a decrease in time spent near the cat compartment, with a complementary increase in time spent at maximum distance, a decrease in transits between these sections, an increase in crouching, and a decrease in grooming and rearing. This pattern of results suggests that morphine may have two opposing effects on defensive behavior, a generalized enhancement, together with a more specific reduction of responses to tactile or painful stimulation. A very widespread pattern of reliable sex or sex x drug effects in the Anxiety/Defense Test Battery was in good agreement with previous reports of sex differences in these tests, with females generally more defensive than males. Consonant with previous findings, no reliable sex differences were found with the Fear/Defense Test Battery, although several values approached an acceptable level of statistical significance.

Animals

Sex effects in defensive behavior: baseline differences and drug interactions.

Female rats consistently show a pattern of differences in defensive behaviors compared to males which parallel the effects of exposure to a nonpainful threat stimulus (cat or cat odor) in the same tests and measures. These indications of greater defensiveness for females are particularly common in situations involving potential, as opposed to actual and present, threat, a factor which probably also reflects ceiling or floor effects in situations involving very intense defensiveness. In addition, pharmacological studies indicate sex differences in the effects of selective serotonin (5-HT) receptor agonists and antagonists on defensive responding. These findings indicate that sex effects must be considered in studies of the pharmacological control of defensive behaviors, and suggest that responsivity to sex effects may be an additional criterion for the suitability of animal models of anxiety.

Aggression

Diazepam changes risk assessment in an anxiety/defense test battery.

An anxiety/defense test battery was designed to assess defensive reactions of laboratory rats to situations associated with nonpainful threat (exposure to a cat). The battery measured three defense patterns, movement inhibition, risk assessment behaviors, and inhibition of nondefensive behaviors, in two tasks. Diazepam (4.0 mg/kg) altered four of five risk assessment measures, but failed to show an anxiolytic effect on movement inhibition, and had minimal and inconsistent effects on inhibition of nondefensive behaviors. The risk assessment changes with diazepam were all consistent with an anxiolytic action of diazepam. These results provide a partial contrast to the general lack of anxiolytic action of diazepam in a fear/defense test battery designed to measure reactions to a discrete, present, threat stimulus, and suggest a greater diazepam effect on risk assessment than on other aspects of defensive responding. Sex differences indicating higher defensiveness for female than male rats were obtained on many of these measures.

Animals

Effects of regional amygdaloid lesions on flight and defensive behaviors of wild black rats (Rattus rattus).

Flight and defensive behaviors of wild black rats (R. rattus) in response to nonpainful threatening stimuli were examined before and after regional amygdaloid lesions. Striking disruption of flight was found following damage to all major amygdaloid regions. In contrast, reduced defensiveness was most consistently associated with damage to cortical and, perhaps, central nuclei. The diffuse organization of flight behavior may result from extensive modality-specific cortical afferents to the amygdala and the varied provided by naturalistics threats. The more restricted representation of defensive attack may have resulted from diminished responsiveness to vibrissal stimulation mediated by medial and dorsomedial amygdaloid structures.

Agonistic Behavior

Effects of scopolamine on antipredator defense reactions in wild and laboratory rats.

Two experiments were designed to investigate the effects of scopolamine hydrobromide (0.25-1.0 mg/kg), and its methyl derivative, on the defensive reactions of rats to nonpainful threat stimuli. In the first experiment, over the dose range studied neither compound significantly altered avoidance, freezing, defensive threat or attack in wild Rattus rattus confronted by the experimenter and other predator-related stimuli. Scopolamine hydrobromide did, however, produce a dose-dependent increase in flight distance; this effect was not seen with the methyl compound, confirming central cholinergic mediation. In the second experiment, no dose of either compound significantly altered the behaviour of Long-Evans rats prior to cat exposure. During cat exposure, however, scopolamine hydrobromide (but not methyl scopolamine) increased the amount of time spent in the vicinity of the cat, increased scanning and rearing, and reduced grooming behaviour. Although reliable, the latter effects were not pronounced. Together, these data do not support a major involvement of central muscarinic receptor mechanisms in the regulation of defensive patterns in wild or laboratory rats.

Aggression

The effects of ethanol and diazepam on reactions to predatory odors.

In a straight alley containing a cat odor stimulus rats show high rates of risk assessment, including flat back approach and stretch attend behaviors oriented toward the threat stimulus and contact with the stimulus. In this situation, diazepam (2.0 and 4.0 mg/kg) significantly reduced risk assessment measures (flat back approach + stretch attend), while not reliably altering control locomotion (curved back). In combination with earlier findings that the same doses of diazepam reliably increased risk assessment from a movement arrest baseline, these results strongly support a behavioral model of anxiety involving predictable nonmonotonic changes in risk assessment as a function of anxiety reduction. In comparison to diazepam, ethanol had less pronounced effects on the Cat Odor Test, as in earlier tasks of reactivity to potential threat. However, reliable dose x time interactions for risk assessment measures suggest ethanol effects similar to those of diazepam but most pronounced in initial stages in the test session.

Animals

Behavioral correlates of chronic dominance-subordination relationships of male rats in a seminatural situation.

Detailed characterization and analysis of intraspecific aggressive and defensive behaviors of rats in mixed sex groups is beginning to provide an understanding of the complex pattern of behavioral and physiological change associated with variation in dominance status. These findings indicate that male subordination dramatically reduces longevity and produces a pattern of behavior changes very similar to the defenses elicited by predatory exposure. In addition, many of these changes are, in detail, isomorphic to important behavioral features of clinical depression.

Animals

The characterization and modelling of antipredator defensive behavior.

The mammalian behavioral antipredator defense systems have been characterized in terms of reactions to present, localizable, threat stimuli: Analysis of the relationship between features of the predator and the environment, and specific defensive behaviors indicates that the latter can be predicted with a high degree of accuracy. A different set of defensive behaviors are seen when rats living in burrow systems are confronted by a predator outside the burrow. Flight to the burrow and immobility inside the burrow are followed by active investigation of the surface where the cat was seen (risk assessment), with all of these accompanied by inhibition of nondefensive behaviors such as eating, drinking, sexual behavior and aggression. Two additional behaviors are described in this context, ultrasonic cries made at a high initial rate (50% time) by animals inside the burrow systems, and declining over 1-2 hours following predator exposure, and, a specific modification of eating patterns when the subjects return to the surface and begin to eat. Eating bouts are shortened, with fewer episodes of continuous eating, interspersed with intervals of scanning of the environment, a vigilance activity previously reported in field research. This analysis of a broad spectrum of defensive behaviors is being used to develop test batteries providing simplified models of these phenomena.

Aggression

Attenuation of defensive threat and attack in wild rats (Rattus rattus) by benzodiazepines.

A battery of tests designed to elicit reactions to a variety of non-painful threat stimuli was used to study the effects of chlordiazepoxide (5-20 mg/kg), diazepam (1-5 mg/kg) and midazolam (1-10 mg/kg) on the defensive repertoire of wild Rattus rattus. The most consistent effect of benzodiazepine treatment, across compounds and tests, was a marked reduction in defensive threat and attack behaviors, with midazolam effective over a wider range of situations. In contrast, effects on freezing and flight reactions were more variable, differing substantially as a function of stimulus context. The general profile of observed changes in defense cannot be explained in terms of either non-specific behavioral suppression or a global reduction in defensiveness. Rather, our findings suggest that benzodiazepines may primarily induce a shift within the defense repertoire.

Aggression

Attack and defense in rodents as ethoexperimental models for the study of emotion.

1. In wild and laboratory rats, offense and defense constitute nonoverlapping behavior patterns seen in response to resource or dominance challenge, or, to predatory, conspecific or environmental threat, respectively. 2. Defensive behaviors are determined by both the threat stimulus and the situation. Defense patterns to discrete, approaching, predators or conspecifics and to nondiscrete, potential, threat have several behaviors in common. However, the latter also includes an important risk assessment complex not seen to discrete, present, threat. Behaviorally and functionally, risk assessment shows considerable similarity to the apprehensive expectation and vigilance and scanning components of generalized anxiety reactions. 3. There are parallels between lower mammal offense and human angry aggression in terms of eliciting stimuli, and a variety of experiential factors including inhibition by fear/pain, and reinforcement effects. 4. A variety of neuroanatomical or pharmacological manipulations have different, often opposite, effects on offense and defense. Differentiation of the two and attention to the specific behaviors involved provide a more precise basis for the use of these patterns as animal models of emotion states.

Aggression