Biomedical subjects

K A Miczek

Publications and source records attributed to K A Miczek.

At least 73 records · Page 4Linked to original sources

PubMed1995

Blood pressure via telemetry during social confrontations in rats: effects of clonidine.

Male Long-Evans rats were implanted with blood pressure transmitters and introduced as intruders for 60 min into the home cage of a reproductively active resident male rat. Physical interaction ended after 3-5 min when the intruder displayed clear submissive behaviors. A protective wire cage was placed over the intruder until the animal was returned to its home cage. Systolic (+29.3 +/- 3.6 mmHg) and diastolic (+25.7 +/- 3.7 mmHg) blood pressures, pulse pressure (+7.3 +/- 2.0 mmHg), and heart rate (+129.0 +/- 12.6 BPM) peaked in the intruder rats during the defeat and did not fully return to control levels until return to the home cage. These acute changes as well as the heart rate and blood pressure baselines did not change when the confrontations were repeated on alternating days for a maximum of three trials per week. Pretreatment with clonidine (0.01, 0.03, 0.06, and 0.1 mg/kg) led to a dose-dependent decrease in the heart rate response but blood pressure was reduced similarly for all doses. We conclude that acute "defeat" can lead to an abrupt, large increase in blood pressure and heart rate in normotensive, Long-Evans rats that is sustained even in the absence of physical contact with the threatening resident. This response is diminished but not prevented by administration of clonidine.

Aggression↗

PubMed1994

Psychomotor stimulant effects of d-amphetamine, MDMA and PCP: aggressive and schedule-controlled behavior in mice.

The objective of the present experiments was to characterize psychomotor stimulant effects of d-amphetamine, methylenedioxymethamphetamine (MDMA) and phencyclidine (PCP) on conditioned performance and on aggressive behavior in mice. In a novel protocol with alternating periods of schedule-controlled responding and aggressive behavior toward an intruder it was possible to assess a range of species-specific agonistic acts, postures, and motor activities as well as response rates and patterns engendered by a multiple Fixed Interval (FI) and Fixed Ratio (FR) schedule within the same animal. Initially, it was confirmed that d-amphetamine and, less reliably, MDMA and PCP, increased FI, but not FR responding in mice. In the next experiment, mice confronted an intruder at the midpoint of the 1-h daily session; following the display of aggressive behavior, the rate of FI responding showed an amphetamine-like increase, whereas only a transient change occurred after non-aggressive encounters. Thirdly, using this new protocol, PCP, d-amphetamine and MDMA altered FI and FR responding in a way that was closely similar to the first experiment. Low PCP and d-amphetamine doses increased aggressive behavior erratically in certain individuals, but not reliably for the group. MDMA dose-dependently decreased aggressive behavior, and all drugs disrupted aggressive behavior at higher doses. The characteristic increases in walking and decreases in rearing after higher doses of PCP and d-amphetamine were greatly attenuated when the intruder was present.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

PubMed1994

Behavioral and autonomic responses to intermittent social stress: differential protection by clonidine and metoprolol.

The present study investigated physiological and pharmacological characteristics of socially "stressed" animals. Specifically, we examined (1) to what degree autonomic and behavioral "stress" reactions during intermittent confrontations between an intruder male adult Long-Evans rat with an aggressive resident undergo habituation, and (2) to what extent the defeat-experienced animal can be protected against these "stress" reactions with clonidine or metoprolol, two adrenergic agents with clinical anxiolytic effects. We developed an acute social stress situation that consisted of initially placing an experimental rat as an intruder into the homecage of a resident while the resident was not present, thereafter permitting brief physical agonistic interactions with the reintroduced resident until the intruder was forced into a submissive supine posture and emitted ultrasonic vocalizations (USV), and eventually exposing the intruder to the resident's threats for one hour, while being shielded from potentially injurious attacks ("threat encounter"). Over the course of the initial 4-weekly threat encounters the acute tachycardia but not the hyperthermic stress responses decreased in magnitude. Following the first three threat encounters core temperature (Tc) was significantly elevated for at least 3 h. The Tc was already elevated when the repeatedly defeated intruder was confronted with the olfactory cues of the resident's cage. This conditioned "anticipatory" hyperthermia developed in the course of the first three confrontations and was paralleled by a decrease in exploratory and motor behavior and by an increase in defensive behaviors and in both types of USV emitted in the "low" (20-30 kHz) and the "high" (31-70 kHz) frequency range. Clonidine (0.01-0.1 mg/kg, IP), an alpha 2-adrenergic agonist and metoprolol, a beta-adrenergic blocker (1.0-10.0 mg/kg, IP), dose-dependently prevented the tachycardic response to stress. Only clonidine, but not metoprolol, also attenuated the rise in Tc during the 1-h agonistic interaction. Clonidine decreased those aspects of motor behavior (e.g. rearing, walking) that are of lesser "cost" for the individual but maintained high levels of defensive reactions and increased the duration of "low" USV. The high doses of clonidine (0.06, 0.1 mg/kg) attenuated the homeostatic regulation and sedated the intruder while exposed to threats during a social confrontation. The absence of attenuation of the high level of defensive behavior and the prolonged "low" USV suggest a stress intensification by the higher doses of clonidine. In conclusion, after the fourth encounter, the autonomic, behavioral and vocal response pattern prior to and during repeated weekly confrontations show no evidence for habituation for the following 6 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

Agonistic Behavior↗

PubMed1994

Diazepam withdrawal: effects of diazepam and gepirone on acoustic startle-induced 22 kHz ultrasonic vocalizations.

It has proven difficult to demonstrate and study the "anxiogenic" quality of drug withdrawal states in animals. Ultrasonic vocalizations (USV) in response to acoustic startle stimuli have shown promise as a measure of affect and may represent "distress" responses during diazepam withdrawal. Three experiments evaluated the association between USV and "distress" by comparing the effects of diazepam as a prototypic benzodiazepine agonist and the putative anxiolytic gepirone with affinity for 5-hydroxytryptamine (5-HT1A) receptors in naive and diazepam-withdrawn subjects. Adult male Long-Evans rats were exposed to acoustic startle sessions consisting of nine 105 dB and nine 115 dB stimuli. USV at 20-30 kHz were readily emitted during startle and often commenced after the third or fourth stimulus presentation. Acutely, intraperitoneal (IP) administration of diazepam (0.1-3 mg/kg) and gepirone (0.1-1 mg/kg) decreased USV dose-dependently without affecting the startle reflex; gepirone also decreased tail flick latency. Startle-induced USV were also sensitive to the "anxiogenic" effects of withdrawal from diazepam exposure (0, 2.5, 5, 10 mg/kg b.i.d. IP x 5 days). Twenty-four hours after the last diazepam injection, rats were hyperreactive to startle stimuli and doubled their rate of USV over vehicle-treated controls. Gepirone (0.1-1 mg/kg IP), but not diazepam (3-20 mg/kg IP) antagonized the increased rate of USV in rats withdrawn from 10 mg/kg b.i.d. diazepam. Diazepam (2.5-10 mg/kg IP) antagonized the increased rate of USV in rats withdrawn from 2.5 mg/kg b.i.d. diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1994

Defeat engenders pentylenetetrazole-appropriate responding in rats: antagonism by midazolam.

Defeat and the threat of defeat by an aggressive conspecific is stressful and may engender an anxiety- or fear-like state in animals; the present experiment investigated whether defeat generalized to the discriminative stimulus properties of PTZ and how benzodiazepine receptors were involved in this generalization. Separate groups of male Long-Evans rats (Rattus norvegicus) were trained to discriminate 20 mg/kg pentylenetetrazole (PTZ) or 0.4 mg/kg midazolam (MDZ) from saline in a two-choice drug-discrimination task. After establishing stimulus control, PTZ- and MDZ-trained rats were exposed to an aggressive conspecific which resulted in defeat, as defined by the display of defensive and submissive postures as well as audible and ultrasonic vocalizations. Administration of saline after defeat resulted in greater than 80% PTZ lever selection in 15 out of 25 PTZ-trained rats; this effect was attenuated through pretreatment with MDZ (1 mg/kg). Furthermore, short-term defeat substitution for the PTZ discriminative stimulus was not accompanied by long-term changes in the post-defeat generalization curves for PTZ and MDZ when compared to pre-defeat generalization curves. Nor did defeat alter the antagonism of PTZ by diazepam (2.5 mg/kg) or MDZ by flumazenil (10 mg/kg). In order further to characterize the necessary features for defeat substitution for the PTZ discriminative stimulus, exposure to a threatening conspecific was also attempted by PTZ-trained rats protected from physical contact with a wire mesh cage. In these tests, saline continued to engender greater than 50% PTZ lever responding in 15 of 25 rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Agonistic Behavior↗

PubMed1994

Ultrasounds emitted by female rats during agonistic interactions: effects of morphine and naltrexone.

Ultrasonic vocalizations may be an expression of the affective pain response in laboratory rodents. The present experiment compared morphine's effects on high (33-60 kHz) and low (20-32 kHz) frequency ultrasonic vocalizations to its effects on a range of unconditioned behavioral responses to aversive stimuli; the influence of estrous cyclicity on morphine sensitivity was also investigated. In experiment 1, naive female Long-Evans rats, selected during estrus or diestrus, received cumulative morphine (1, 3, 6, 10 mg/kg SC) or saline, and in experiment 2, rats were pretreated with naltrexone (0.1 mg/kg IP) 5 min before morphine (17, 30, 60, 100 mg/kg SC). The following endopoints were measured 20-25 min post-injection: (1) tail flick latency; (2) ultrasonic and audible vocalizations; (3) the behavioral response to aggressive attack; and (4) locomotor activity. Following a brief exposure to an attack, rats were threatened by an aggressor but protected from further attack by a wire mesh cage (30 x 21.5 x 20 cm), thereby allowing for continued behavioral and vocal measurement without the risk of physical injury; video and audio recordings were made of the attack encounter and a subset of the protected encounter (1 min). The endpoint most potently and specifically modulated by morphine was high frequency ultrasounds. The rate of high frequency calling varied as a function of the estrous cycle, supporting gonadal hormone modulation of ultrasonic vocalizations. Low frequency ultrasounds, by contrast, were relatively insensitive to opiate manipulation and were less influenced by estrous cyclicity. High frequency vocalizations may be a more sensitive indication of the affective response to an attacking conspecific that low frequency calls.(ABSTRACT TRUNCATED AT 250 WORDS)

Agonistic Behavior↗

PubMed1994

Neurobiological mechanisms controlling aggression: preclinical developments for pharmacotherapeutic interventions.

Current pharmacotherapeutic approaches to the management of violent and aggressive behavior rely mostly on agents that act as receptor agonists or antagonists at subtypes of brain dopaminergic, GABAergic, and serotonergic receptors. Ethological experimental studies in animals have shown that drugs may modulate aggression by inhibiting motor activity, by distorting aggression-provoking or -inhibiting signals, by fragmenting behavioral sequences or temporal patterning, or by increasing the rate and intensity of aggressive acts. Evidence from animal studies points to large changes in selected brain dopamine, serotonin, and GABA systems during and following aggressive and defensive behavior. However, the specificity of drugs that are currently used to control aggressive behavior through their action as agonists or antagonists at subtypes of dopamine, serotonin or GABA receptors continues to be of concern. Similar to the effects of widely used traditional neuroleptics that nonselectively antagonize dopamine receptors, the range of behaviors which is suppressed by either D1 or D2 receptor antagonists is pervasive. At present, systemic administration of dopamine receptor antagonists in animal preparations does not target aggression-specific mechanisms. The GABAA/Benzodiazepine/Chloride ionophore receptor complex is implicated in the aggression-heightening effects of alcohol and benzodiazepines. Although early reports focused on the "taming" effects of benzodiazepine anxiolytics, low doses may enhance aggression in both animals and humans. Benzodiazepine antagonists block heightened aggression after low doses of alcohol or benzodiazepines. Agonists at certain 5-HT1 receptor subtypes such as eltoprazine are potently effective in reducing aggressive behavior of males and females of various animal species under conditions that promote charging offensive-type aggression, without adversely affecting nonaggressive components of the behavioral repertoire. However, recent reports indicate that eltoprazine and related compounds may potentiate anxiety reactions in rodents, and question the behavioral specificity of these substances. Opioid receptor antagonists modulate primarily physiological and behavioral responses of defense and submission. Defeated animals show tolerance to opiate analgesia and withdrawal responses upon challenge with opioid receptor antagonists. Defensive and submissive vocalizations are potently blocked by opioid peptides. Substances that target specific receptor subtypes at serotonergic, GABAergic and opioidergic synapses are most promising for the selective modification of aggressive, defensive and submissive behavior patterns.

Aggression↗

PubMed1993

"Anxiolytic" and "anxiogenic" benzodiazepines and beta-carbolines: effects on aggressive and social behavior in rats and squirrel monkeys.

Ethopharmacological studies on the behavior of socially housed rats and squirrel monkeys were conducted to explore the role of the benzodiazepine GABAA-coupled ionophore receptor complex in aggressive and social interactions. Benzodiazepine receptor (BZR) antagonists, ZK 93426 (1-10 mg/kg) and flumazenil (3-10 mg/kg), the partial agonist, ZK 91296 (1-10 mg/kg) and the partial inverse agonists Ro 15-4513 (0.3-10 mg/kg), were administered to (1) squirrel monkeys prior to 1 h focal observations within established social groups or to (2) resident male rats before confrontations with a naive male intruder in their home cage for 5 min. Aggression was modified in a similar manner in both species, although squirrel monkeys were more sensitive to BZR challenges. Specifically, resident male rats showed dose dependent reductions in attack bites directed at intruder males that were significant at the highest dose of ZK 93426 (10 mg/kg). In squirrel monkeys, ZK 93426 (3 and 10 mg/kg) reduced aggressive grasps, threats and displays, as well as reducing the duration of being the target of aggression from untreated group members (1-10 mg/kg). The BZR partial agonist, ZK 91296 and the antagonist, flumazenil produced few effects on social behavior, low and high intensity aggression and motor activity in both species. Flumazenil (10-30 mg/kg) and ZK 91296 (10 mg/kg), but not ZK 93426, produced significant increases in foraging and feeding behaviors in squirrel monkeys. The hyperphagic effects of ZK 91296 and flumazenil, that are typical of BZR agonists compounds, were not observed in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

PubMed1993

Morphine attenuates ultrasonic vocalization during agonistic encounters in adult male rats.

Ultrasonic vocalizations (USV) in rats may communicate "affective" states during pain, sex and aggression. This proposal was evaluated in an experiment with adult male Long-Evans rats during agonistic encounters; specifically, morphine and naltrexone effects were studied on different types of USV by intruder rats exposed to resident attacks and to "threat of attacks" (i.e., intruder residing within the home cage of the resident but prevented from physical contact by a wire mesh cage). Intruders readily emitted USV during agonistic encounters. These calls consisted primarily of two distinct distributions of pure tone whistles: 0.3-3 s, 19-32 kHz ("low") calls and 0.02-0.3 s, 32-64 kHz ("high") calls. Sonographic analysis revealed a considerable repertoire of frequency modulated calls. Different types of vocalizations proved to be differentially sensitive to the opiate treatments: morphine (1-10 mg/kg SC) dose-dependently decreased the rate, duration and pitch of both low and high frequency USV during the threat of attack; this decrease in rate and duration measures was naltrexone-reversible (0.1 mg/kg IP). Interestingly, audible vocalizations were also emitted but were unaffected by morphine in this dose range. Concomitant with the decrease in USV after morphine was a dose-dependent decrease in rearing, walking and nasal contact behavior with increases in submissive crouch behavior and tail flick analgesia. The decreases in rate and duration of both low and high USV and the pitch of specific frequency modulated calls after morphine administration may reflect an attenuation of affective aspects of pain, and the many characteristics of US (rate, duration, pitch, frequency modulation, pre-and suffix attributes and temporal structure) point to potentially diverse functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Agonistic Behavior↗

PubMed1993

Prevention of the pro-aggressive effects of alcohol in rats and squirrel monkeys by benzodiazepine receptor antagonists.

Pharmacological manipulations at the benzodiazepine-GABAA-chloride ionophore receptor complex modify some of the behavioral and physiological actions of alcohol (ethanol). The interactions between alcohol, benzodiazepines and aggression were examined in similar ethopharmacological studies in squirrel monkeys and in rats in confrontations with conspecifics. Dominant male squirrel monkeys were tested (1) within their social groups, and (2) in dyadic confrontations with "rival" males from a different social group, and resident male rats were tested in their home cage in confrontations with an inexperienced male intruder. Low doses of alcohol (0.1-0.3 g/kg) increased aggressive behaviors in dominant squirrel monkeys and a subgroup of resident rats, whereas high doses of alcohol (1-3 g/kg) decreased aggression and produced marked motor incoordination. Individuals that showed alcohol-enhanced aggression were selected, and pretreated with benzodiazepine antagonists (flumazenil, ZK 93426) prior to alcohol administration. Both ZK 93426 (3 mg/kg) and flumazenil (10 mg/kg) blocked the aggression-enhancing effects of alcohol in dominant squirrel monkeys and resident rats in confrontations with conspecifics. Neither compound altered the reductions in aggression and increases in inactivity produced by high doses of alcohol. Interestingly, agonist-like increased feeding and inverse agonist-like reductions in social behaviors were observed simultaneously at the same dose of flumazenil, in the same individual and testing situation. ZK 93426 did not alter feeding but also reduced social behaviors. The two antagonists were also not equipotent in their interactions with alcohol. ZK 93426 reduced alcohol-induced motor incoordination in squirrel monkeys, whereas flumazenil did not. In fact, flumazenil potentiated the effects of low doses of alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

PubMed1993

Diazepam and gepirone selectively attenuate either 20-32 or 32-64 kHz ultrasonic vocalizations during aggressive encounters.

Ultrasonic vocalizations (USV) in rats may communicate "affective" states, as they occur only in highly significant behavioral contexts such as during sex, aggression, exposure to painful or startling events. This proposal was evaluated in an experiment with adult male Long-Evans rats during agonistic encounters; specifically, the effects of diazepam, flumazenil and gepirone were studied on different types of USV emitted by intruder rats exposed to resident attacks and to "threat of attacks" (i.e., intruder protected within the home cage of the resident by a wire mesh cage). USV were readily emitted during agonistic encounters and consisted primarily of two distributions of pure tone whistles: 0.3- to 3-s, 20- to 32-kHz ("low") signals and 0.02- to 0.3-s, 32- to 64-kHz ("high") signals. A considerable repertoire of frequency modulated signals was observed and proved to be sensitive to the anxiolytic treatments. Diazepam (1-6 mg/kg) dose-dependently decreased high frequency USV during the threat of attack and decreased the mean pitch of the most predominant vocalizations but did not affect low frequency USV or the audible squeals (AS) in response to bites. Gepirone (0.3-6 mg/kg) dose-dependently decreased low frequency USV and did not affect high frequency USV or AS. Responses to thermal pain stimuli remained unaltered by all drugs, while walking duration was decreased and crouch postures were increased after diazepam but not after gepirone administration. Gepirone in the present dose range had minimal effects on submissive, exploratory and locomotor behaviors. The pattern of results is consistent with the proposal that low frequency USV reflect a heightened affective state which is ameliorated with 5HT1A but not benzodiazepine anxiolytics, and suggests that the suppression of high frequency USV in reaction to attacks or threats coincides with the sedative or muscle relaxant properties of these compounds.

Aggression↗

PubMed1993

Automatic quantification of withdrawal from 5-day diazepam in rats: ultrasonic distress vocalizations and hyperreflexia to acoustic startle stimuli.

The purpose of the present work was to develop an objective and precise method to quantify withdrawal responses from anxiolytics relying on ethologically valid responses. Behavioral effects of diazepam withdrawal in rats are automatically measured that appear to correspond to clinically relevant disturbances in affective and sensory-motor functions. Ultrasonic vocalizations and startle reflexes in response to acoustic stimuli were measured as indices of withdrawal 24 h after 5 days of 2.5, 5 or 10 mg/kg diazepam, b.i.d., IP in male Long-Evans rats. About 60% of male rats emit 22-26 kHz ultrasonic calls when exposed to acoustic startle stimuli (18 presentations, 9 at 105 dB and 9 at 115 dB, each 30 s apart on average). Diazepam-withdrawn rats exhibited startle responses with larger maximal and average amplitude and emitted more frequent 22-26 kHz ultrasonic vocalizations than vehicle-treated control animals. The magnitude of the withdrawal changes in ultrasonic calls and in startle reflex amplitude increased significantly already at the low 2.5 mg/kg diazepam dose in spite of considerable individual variability. The increased ultrasound rates during diazepam withdrawal contrast with the suppressive effects of acutely administered diazepam in drug-naive rats. The current methodology offers the opportunity to more adequately characterize withdrawal from anxiolytic substances in a quantitative, objective and automated manner.

Acoustic Stimulation↗

PubMed1993

Long-term impairment of autonomic circadian rhythms after brief intermittent social stress.

This experiment was designed to examine the short- and long-term behavioral, cardiovascular, and thermoregulatory responses to brief intermittent agonistic confrontation in rats. The experimental procedure involves resident-intruder confrontations consisting of a 10-min period during which both animals are separated in the home cage of the resident, followed by a brief physical encounter leading to defeat of the intruder and a 10-min period, when the intruder was alone in the home cage of the resident. These 30-min-long confrontations were repeated on 5 consecutive days. Before the first confrontation with a resident, an intruder rat's telemetered heart rate and core temperature show a stable circadian rhythm that is entrained by the light cycle. Acutely, the confrontations produce immediate and large tachycardia and hyperthermia in intruders. A decrease in amplitude of the circadian rhythms for heart rate and core temperature, as detected by cosinor analysis, persists for at least 10 days after the last of five daily brief confrontations with the resident. The defensive upright posture is nearly absent during the first exploration of the resident's home cage, but is displayed by the intruder for one-third of the available time before and after the fifth defeat. Intermittent brief social stress is sufficient to induce profound changes in defensive behavior and long-lasting depression of circadian rhythmicity that persist for weeks.

Agonistic Behavior↗

PubMed1993

Blockade of pituitary-adrenal axis activation induced by peripheral immunoneutralization of corticotropin-releasing factor does not affect the behavioral response to social defeat stress in rats.

Specific in vivo immunoneutralization of hypophysiotrophic corticotropin-releasing factor (CRF) and vasopressin (AVP) was used to investigate the respective roles of these circulating peptides in the hormonal response to a social stressor in Wistar rats. The effect of peripheral immunoneutralization on the behavioral response to the same social stressor was also studied. Stress was produced using social defeat in a resident-intruder paradigm, in which an intruder male rat, equipped with an indwelling IV catheter, was confronted with a dominant resident male rat. To minimize the physical component of the agonistic interaction, the intruder was protected immediately after the resident's first attack in a Plexiglas/wire-mesh enclosure. In the following time interval, the resident continued to threaten the protected intruder, which showed a significant increase in plasma immunoreactive adrenocorticotropic hormone (ACTH) and corticosterone levels compared to those measured in rats exposed to a control procedure. The hypothalamo-pituitary-adrenal (HPA) axis response to social defeat stress was totally abolished by pretreatment with an anti-CRF serum (0.3 ml IV) but not an anti-AVP serum (0.75 ml IV). An animal model for anxiety in rodents, the elevated plus-maze, was used to study the emotional response to social defeat stress in rats given anti-CRF serum or normal serum. A significant reduction of open-arm exploration was observed in defeated rats tested 10 min after the end of the agonistic interaction when compared with control animals for all antisera treatment group, indicating an "anxiogenic-like" emotional response to the social defeat stress. Pretreatment with anti-CRF serum did not affect the behavioral performance of defeated and control rats. These results suggest that: 1) social defeat stress produced an activation of the HPA axis in the rat which is mediated by hypophysiotrophic CRF but not AVP; and 2) the peripheral activation of the HPA axis induced by social defeat stress is not involved in the behavioral response to stress as measured in the elevated plus-maze.

Adrenocorticotropic Hormone↗

PubMed1993

Ultrasounds during agonistic interactions between female rats (Rattus norvegicus).

Defensive and vocal behaviors of 18 female Long-Evans rats (Rattus norvegicus) in encounters with aggressive, lactating conspecifics were examined in order to determine if female rats emit ultrasounds during agonistic interactions and to characterize any such calls. The subjects, selected during estrus or diestrus, were exposed to 1-min attacks at 25-min intervals. Between attacks the subjects were threatened by the aggressor but protected by a wire-mesh cage. Female rats emitted both high- (32-60 kHz) and low-frequency (20-32 kHz) ultrasonic calls in agonistic encounters, with the rate of high-frequency calls enhanced during estrus. Low-frequency ultrasounds were shorter in duration and higher in frequency than those emitted by male rats in similar conditions. We conclude that female rats emit ultrasonic calls during defensive responding and that the characteristics and rate of calling vary as functions of sex and gonadal hormone state.

Agonistic Behavior↗

PubMed1993

Alcohol, benzodiazepine-GABAA receptor complex and aggression: ethological analysis of individual differences in rodents and primates.

Research in animals has only recently been successful in reliably mimicking the long-established link between alcohol and heightened aggressive behavior. The present review highlights the large individual differences in the effects of acute low alcohol doses on aggressive behavior in rodent and primate species, paralleling the human condition. Subpopulations of both species show reliable and repeatable enhancement of aggressive behavior when administered low, acute alcohol doses. Statistical analysis of the temporal patterns of aggressive behavior indicate that alcohol prolongs aggressive bouts or "bursts" and increases the number of aggressive behaviors within each burst. However, the latency to initiate attack and the time between aggressive bursts are relatively unaltered by alcohol. These alcohol-induced increases in aggression can be potentiated by benzodiazepine agonists and prevented by antagonists. In addition, highly aggressive animals can be differentiated from nonaggressive ones at the GABAA-benzodiazepine receptor complex. These data suggest an important link between alcohol, aggression and the GABAA-benzodiazepine receptor complex.

Aggression↗

PubMed1992

Phenobarbital-responsive episodic dyscontrol (rage) in dogs.

Episodic dyscontrol (rage) was diagnosed from the clinical history, electroencephalographic findings, and response to oral treatment with phenobarbital in 3 dogs. Clinical features included a mood change heralding aggressive incidents, explosive aggression directed at people or objects, and a postaggressive phase characterized by lethargy and lack of responsiveness. Abnormal electroencephalographic findings included spike activity in the temporal recordings. All 3 dogs responded well to anticonvulsant medication with phenobarbital.

Aggression↗

PubMed1992

Corticotropin-releasing factor antagonist reduces emotionality in socially defeated rats via direct neurotropic action.

Introduction of a socially naive male rat into the home territory of a resident counterpart results in agonistic interactions, leading to the rapid social defeat of the intruder. Exposure to the aggressive resident produces a stress-response profile consisting of neuroendocrine activation and coping behaviors such as submission. The present studies examined the dependence of these adaptive responses on endogenous brain Corticotropin-Releasing Factor (CRF), a peptide hormone known to coordinate neuronally mediated- and pituitary-adrenal responses to stress. The Elevated Plus-Maze was employed as an animal model of emotionality in which stressors reduce subsequent exploration of open maze arms without walls in favor of enclosed maze arms. A CRF antagonist, alpha-hel CRF9-41, administered intracerebroventricularly (5 and 25 micrograms i.c.v.) immediately post-stress and 5 min prior to maze testing reversed the heightened emotionality produced by the resident exposure stressor. This action paralleled that of an anxiolytic dose of the short-acting benzodiazepine, midazolam (1.5 mg/kg i.p.). Intra-amygdaloid administration of lower doses of the CRF antagonist (125, 250 and 500 ng i.c.) also reversed, dose-dependently, the effect of exposure to an aggressive resident without altering the behavior of unstressed control animals. Further, the enhanced release of ACTH and corticosterone following social conflict was not modified over the short term by the intra-amygdaloid dose of CRF antagonist (250 ng i.c.) which was effective in reversing stress-induced hyper-emotionality. These results suggest that limbic system CRF substrates exert an anxiogenic effect on the exploratory behavior of socially defeated rats via a pituitary-adrenal-independent mechanism.

Adrenocorticotropic Hormone↗