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W Tornatzky

Publications and source records attributed to W Tornatzky.

15 recordsLinked to original sources
PubMed2003

Accumbal dopamine and serotonin in anticipation of the next aggressive episode in rats.

Autonomic and limbic neural activities are linked to aggressive behavior, and it is hypothesized that activities in the cardiovascular and monoaminergic systems play a role in preparing for an aggressive challenge. The objective was to learn about the emergence of monoamine activity in nucleus accumbens before an aggressive confrontation that was omitted at the regular time of occurrence, dissociating the motoric from the aminergic activity. Dopamine, serotonin, heart rate and behavioral activity were monitored before, during and after a single 10-min confrontation in resident male Long-Evans rats fitted with a microdialysis probe in the n. accumbens and with a telemetry sender (experiment 1). DA, but not 5-HT efflux, was confirmed to increase in n. accumbens during and after a single aggressive episode. In aggressive males that confronted an opponent daily for 10 days (experiment 2) heart rate rose 1 h before the regularly scheduled encounter relative to control rats, as measured on day 11 in the absence of any aggression. Concurrently, DA levels increased by 60-70% over baseline levels and 5-HT levels decreased by 30-35% compared to baseline levels. These changes were sustained over 1 h, and contrasted with no significant changes in DA, 5-HT, heart rate or behavioral activity in control rats. The rise in mesolimbic DA appears to be significant in anticipating the physiological and behavioral demands of an aggressive episode, and the fall in 5-HT in its termination, dissociated from the actual execution of the behavior.

Aggression↗
PubMed2001

Zolpidem, triazolam, and diazepam decrease distress vocalizations in mouse pups: differential antagonism by flumazenil and beta-Carboline-3-carboxylate-t-butyl ester (beta-CCt).

In response to stressful events, neonatal mice emit ultrasonic vocalizations (USVs), which are suppressed by BZ agonists. The present study examined the role of the benzodiazepine/alpha1 (BZ/alpha1) receptor subtype in the suppression engendered by the BZ/alpha1-preferring agonist zolpidem and the nonselective BZ agonists triazolam and diazepam. The role of BZ receptor subtypes was explored further by conducting antagonism studies using the BZ/alpha1-preferring antagonist beta-carboline-3-carboxylate-t-butyl ester (beta-CCt), in comparison with the nonselective BZ antagonist flumazenil. Mouse pups (CFW strain) were separated from their dam and littermates at day 7, and placed for 4 min in a test chamber with reduced ambient temperature (19 +/- 1 degrees C) for recording USVs, motor incoordination (measured as a pup rolling on its back per grid cross), and body temperature. Zolpidem, triazolam, and diazepam suppressed USVs in a dose-dependent manner, concomitant with increases in incoordination and augmentation of hypothermia. These effects of the three BZ agonists were blocked by flumazenil in a manner consistent with surmountable antagonism. The ability of zolpidem, but not triazolam or diazepam, to suppress USVs and augment hypothermia was antagonized by beta-CCt, whereas the increase in motor incoordination engendered by zolpidem, triazolam, and diazepam was not sensitive to beta-CCt administration. Collectively, these results suggest that zolpidem suppresses distress USVs in mouse pups by a mechanism distinct from that of typical BZs. Furthermore, suppression of distress USVs by zolpidem may involve BZ/alpha1 receptors and a nonanxiolytic mechanism, such as hypothermia.

Animals↗
PubMed2000

Cocaine self-administration "binges": transition from behavioral and autonomic regulation toward homeostatic dysregulation in rats.

BACKGROUND: An essential feature of cocaine addiction is the breakdown to control or regulate drug intake. OBJECTIVE: The present studies aimed to examine the transition from regulated intravenous cocaine reinforcement to a more unpredictable, chaotic pattern of cocaine self-administration in rats that were given continuous access to the drug. Autonomic activity was continuously monitored via biotelemetry senders for heart-rate and core temperature before, during and after the cocaine "binges", in an attempt to characterize the breakdown of homeostatic regulation. METHODS: After Long-Evans rats were fitted with intravenous catheters and intraperitoneal telemetry senders, they acquired cocaine self-administration with each fifth lever press being reinforced by a 0.25 mg cocaine infusion. Rats self-administered 15 cocaine infusions daily at stable rates for ca. 2-3 weeks, when continuous access periods ("binges") of 26 and 72 h were scheduled, with a 3-week cocaine-free period between and following the two "binges". RESULTS: A distinctive pattern of cocaine self-administration emerged during the "binges" that consisted of (1) an initial loading phase, (2) stable, predictable inter-infusion intervals for up to 8-10 h, termed "regulatory phase", (3) increased variability in inter-fusion intervals, mostly beginning at 22-24 h of continuous access. During the first half of the 72-h "binge", the autonomic activities remained elevated, showed a greatly constrained variability, and the characteristic circadian rhythmicity was substantially decreased. The average cocaine intake (6.8+/-0.5 mg/kg per hour) during the "regulatory" phase did not change during the subsequent phases. Following the 72-h "binge", the amplitude of autonomic circadian rhythms remained attenuated for more than 2 weeks. In a separate set of animals, the dose effect of inter-infusion intervals following the self-administered infusion was similar during a variable dose protocol, scheduled in an early and a late phase of a 30-h long "binge". CONCLUSIONS: The homeostatic dysregulation during the "binge" as evidenced by the diminished capacity of autonomic functions to vary is accompanied by emerging irregularities in the pattern of cocaine self-administration.

Animals↗
PubMed1999

Repeated limited access to i.v. cocaine self-administration: conditioned autonomic rhythmicity illustrating "predictive homeostasis".

RATIONALE: Regular cocaine self-administration may act as a "Zeitgeber" in animals and humans, and physiological rhythms may peak at the time when the drug is usually self-administered. OBJECTIVE: To investigate whether or not daily sessions of cocaine self-administration for 2 weeks would synchronize autonomic rhythms to the time of daily access. METHODS: Two weeks after implant of a jugular catheter and telemetry sender, each rat's heart-rate (HR) and core temperature (Tc) rhythms were well entrained to the 12:12-h light:dark cycle (lights off: 0900 hours). For the next 2 weeks rats self-administered cocaine during daily sessions at 1300 hours. The circadian and ultradian oscillations of HR and Tc recorded during the 3 days after the last self-administration (SA) session were quantified by multi-oscillator cosinor analysis. RESULTS: The HR and Tc were elevated during the initial 0.25 mg cocaine infusions of the daily session. This initial tachycardia disappeared as cocaine continued to be self-administered in accumulating amounts, while the locomotor activity remained elevated. After the last SA session the peak (acrophase) of the two cycles/day component in HR and Tc rhythms aligned to the time of day when cocaine self-administration had previously been scheduled. The amplitude of the circadian and ultradian HR and Tc oscillations as well as their circadian acrophase were not impacted by repeated daily time-limited cocaine self-administration. CONCLUSIONS: Cocaine controls the behavior and autonomic functions of rats self-administering limited amounts of cocaine during regular daily sessions, and this controlling influence extends beyond the last daily access period.

Animals↗
PubMed1998

Recurrent aggressive episodes entrain ultradian heart rate and core temperature rhythms.

The present study was designed to investigate the effects of recurrent aggressive episodes on the synchrony of autonomic circadian and ultradian rhythms. Eight aggressive male rats were entrained to a reverse 12 h:12 h light-dark cycle and then implanted with telemetry senders to continuously monitor heart rate (HR) and core temperature (Tc). The amplitude and the time of the peak (acrophase) for each of the circadian and ultradian oscillations were quantified by nonlinear, least-squares, multioscillator cosinor analysis that included the first four harmonics of the circadian rhythm. After recovery from surgery, the 3- and 5-cycle/day ultradian rhythms of HR and Tc were the prominent ultradian components that were synchronized to the light-dark cycle. First, the resident males confronted a male intruder daily at lights-off (0800 hours) for a period of 3 weeks. Second, after a 3-week recovery period, 15 daily aggressive confrontations were scheduled, with the intruders being introduced at 1200 hours. During the course of the confrontations the amplitude of 3- and 5-cycle/day oscillations in HR and Tc decreased, whereas the hemicircadian (2 cycles/day) rhythm amplitude doubled with minor changes of the circadian amplitude. The hemicircadian acrophase coincided with the time of the confrontation most clearly, and this alignment lasted for more than 1 week after the last social confrontation, even in the absence of a reminder. We interpret the synchronization of the hemicircadian acrophases to the time point of social confrontations as anticipating the physiological demands of the aggressive encounters.

Activity Cycles↗
PubMed1997

Alcohol, GABAA-benzodiazepine receptor complex, and aggression.

Neurobiological investigations have become productive since experimental protocols were developed that engender large increases in aggressive behavior after acute alcohol challenges in individual experimental animals. Recent developments extended the heightened aggressive behavior to rats that self-administered alcohol shortly before the social confrontation. Quantitative ethological analysis revealed that alcohol prolongs "bursts" of aggressive acts and displays and disrupts communication between the aggressive animal and the opponent who defends, submits, or flees. Pharmacological modulation of the GABAA receptor with benzodiazepine agonists and neuroactive steroids results in dose-dependent biphasic changes in aggressive behavior that mimic the dose-effect function of alcohol; benzodiazepines potentiate the aggression-heightening effects of alcohol as well as the behaviorally suppressive effects; and antagonists at benzodiazepine receptors prevented the aggression-heightening effects of alcohol. The maturational and experiential origins for potentially distinctive GABAA receptor characteristics in individuals who exhibit heightened aggressive behavior await identification.

Aggression↗
PubMed1996

Stress induced disorganization of circadian and ultradian rhythms: comparisons of effects of surgery and social stress.

Persistent autonomic disturbances following stressful events suggest that the rhythmical nature of homeostatic functioning may be disrupted by these experiences. We assessed the effects of two different stressors on circadian and ultradian rhythms of Long-Evans rats by using nonlinear multi-oscillator cosinor analysis. Heart rate and intraperitoneal temperature were monitored continuously in 5-min intervals in two groups of animals via radio-telemetry for 15 days after surgery (n = 9) and 15 days following social defeat (n = 6). Circadian amplitude of heart rate and temperature increased significantly for the first nine days of the recovery from surgery but only circadian temperature amplitude increased following social defeat. Circadian acrophase of temperature but not heart rate changed significantly for a similar period following the surgery but not after the social defeat. A mathematical model incorporating the first five harmonics of the circadian rhythm was found to fit the data significantly better than a circadian model alone with rhythms of 3 and 5 cycles/day in temperature and heart rate entraining significantly to the light-dark schedule. Full recovery of the circadian and ultradian rhythms did not occur until a minimum of nine to twelve days after surgery or social defeat. The results suggest that rhythms with multiple periodicities are involved in homeostatic functioning and that models incorporating these rhythms may aid in understanding an organisms adaptive response to surgical intervention and social defeat, long after the challenges have terminated.

Activity Cycles↗
PubMed1995

Alcohol, anxiolytics and social stress in rats.

The main objective was to compare the anxiolytic-like profiles of alcohol, diazepam and gepirone along the stress intensity gradient which characterizes consecutive phases of a social confrontation. The acute social stress situation consisted of initially placing the experimental rat as an intruder into the homecage of a resident while the resident was not present, termed the "anticipatory" phase, thereafter permitting brief physical agonistic interactions with the re-introduced 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 1 h, while being shielded from potential injurious attacks. The hyperthermia, measured via telemetry, in the "anticipatory" phase prior to defeat and in reaction to threats, was decreased by alcohol, gepirone and diazepam; alcohol and gepirone were also effective in attenuating "anticipatory" tachycardia. Alcohol, like gepirone and diazepam, also decreased defensive responses and ultrasonic vocalizations in the "anticipatory" phase of the confrontation, but none of these drugs affected defensive reactions to threats which immediately followed defeat. Gepirone had no systematic sedative effects throughout the confrontation; infact, it dose-dependently reduced the stress-induced suppression of locomotor activity during the "anticipatory" phase. In contrast, at higher doses, alcohol as well as diazepam had marked sedative effects as evidenced by several behavioral parameters (i.e. lie, crouch, walk). The anxiolytic-like profile of hyperthermia, tachycardia, USV and defensive behavior in the "anticipatory" phase of the confrontation by alcohol, gepirone and diazepam contrasted with the lack thereof during the more intense reactive phase. This differential pattern of effects appears to be relevant to the clinical distinctions between anticipatory anxiety and other affective disturbances.

Animals↗
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

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↗
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

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

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↗
PubMed1992

Alcohol and "bursts" of aggressive behavior: ethological analysis of individual differences in rats.

A quantitative ethological analysis of rodent aggression was performed in order to characterize the aggression-heightening effects of alcohol in certain individuals. In dyadic confrontations, a resident rat pursues, threatens and attacks an intruder, who reacts with defensive, flight and submissive behaviors. The behavioral data from five series of experiments conducted from 1984 through 1989 were subjected to a lag sequential analysis that identified highly predictable sequences of aggressive behavior, and to interval analysis that delineated a burst pattern of aggressive behavior. These analyses revealed a distinct behavioral sequence of pursuit----sideways threat----attack bite----aggressive posture that occurs in bursts with an inter-event interval of less than 6.6 s. In the total population, alcohol heightened attack behavior at low acute doses (0.1, 0.3, 1.0 g/kg) in 47% of the animals (n = 44), suppressed reliably attack behavior in another 25% (0.1-3.0 g/kg; n = 23) and had unreliable effects in the remaining 28% (n = 24). The peak enhancement of aggressive behavior was seen over more than a log cycle of alcohol doses (0.1, 0.3 or 1.0 g/kg) in different individuals. In an additional group of rats (n = 20), individuals were identified according to whether or not acute low alcohol doses enhanced or suppressed the frequency of attack bites. In the subgroup of five rats who doubled their attack frequency upon acute alcohol challenge, this aggression-heightening effect was confirmed on repeated occasions. The aggression-heightening effects of alcohol were seen during the high-rate interactions in the initial phase of the confrontation and particularly during the lower level of fighting later on. Regardless of alcohol dose and subgroup, the highly predictable sequence of pursuit----sideways threat----attack bite----aggressive posture remained intact as long as the individual was able to fight. The present analysis identifies those individuals in whom low alcohol doses increase the frequency of attack behavior, the number of aggressive elements in bursts and particularly the "time in burst". Alcohol produces these changes without altering the latency to initiate aggressive behavior, the rate of aggressive behavior within a burst or the number of bursts in an encounter. Alcohol may lengthen aggressive bursts by preventing termination of longer aggressive sequences rather than by altering the initiation of this behavior.

Aggression↗