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K A Miczek

Publications and source records attributed to K A Miczek.

At least 109 records · Page 6Linked to original sources
PubMed1988

Analgesia in defeated mice: evidence for mediation via central rather than pituitary or adrenal endogenous opioid peptides.

Mice subjected to defeat in a social conflict paradigm display an analgesic response that is apparently mediated by endogenous opioids. It is blocked by naloxone and shows full cross-tolerance to and from morphine. The present study investigated the contribution of sources of endogenous opioids outside of the central nervous system, namely the pituitary and adrenal glands. Treatment known to enhance (metyrapone pretreatment), reduce (2% saline in the drinking water) or block (dexamethasone pretreatment) the release of beta-endorphin from the anterior pituitary did not affect the display of analgesia in defeated mice. Similarly, treatments known to enhance (reserpine pretreatment) or block release of enkephalins (removal of the adrenals or hexamethonium pretreatment) from the adrenal medulla also failed to influence defeat-induced analgesia in the expected manner. If anything, adrenalectomy enhanced and reserpine pretreatment suppressed the analgesic response to defeat. The data are discussed in terms of providing evidence that defeat-induced analgesia is mediated primarily by endogenous opioids released and acting within the central nervous system.

Animals↗
PubMed1987

Analgesia and decrement in operant performance in socially defeated mice: selective cross-tolerance to morphine and antagonism by naltrexone.

During a social confrontation between a resident and an intruder mouse, only the submissive or defeated intruder shows an opioid-mediated analgesia to which tolerance develops. We investigated the altered morphine responsiveness after different kinds of social experiences. Mice were assessed for performance of operant behavior under the control of a fixed ratio schedule of positive reinforcement as well as for the tail flick response to a heat stimulus before and after one or five consecutive social confrontations. The dose-effect curves for morphine's suppression of schedule-controlled behavior were closely similar before and after defeat in a single or in five social confrontations. However, the concurrently measured response to pain in the tail flick assay produced morphine dose-effect curves that were shifted to the right after defeat in one or five social confrontations. Four to six times higher doses of morphine were necessary to produce analgesia in mice that were defeated in five social confrontations. Naltrexone (1 mg/kg, ip) antagonized the suppressive effects of morphine (10 mg/kg, ip) on rate of responding and the analgesic effects. Naltrexone also blocked the development of analgesia in mice that were defeated for the first time in a social confrontation, but did not prevent the suppressive effects on rate of responding. Specific social experiences such as defeat in a social confrontation appear to alter endogenous opioid process that mediate analgesia; these processes differ from those that suppress positively reinforced behavior. The differential development of morphine tolerance to the analgesic effects, but not the rate-decreasing effects as well as the differential naltrexone antagonism of both effects may indicate the involvement of opioid and non-opioid mechanisms.

Aggression↗
PubMed1986

Aggression during morphine withdrawal: effects of method of withdrawal, fighting experience, and social role.

Offensive and defensive components of aggressive behavior were determined in resident and intruder mice. Withdrawal aggression was measured after the removal of a subcutaneous morphine pellet or after precipitation by naloxone in naive mice and after removal of a morphine pellet in mice with prior fighting experience. In naive mice, removal of a morphine pellet led to increases in attack bites and threats but naloxone-precipitated withdrawal led to decreases in these behaviors and to increases in defensive posturing, escape attempts and vocalizations. Prior fighting experience abolished the enhanced attack behaviors of resident mice following morphine pellet removal, but led to heightened defensive behavior in intruder mice. The behavior of intruder mice appeared more sensitive to naloxone administration than the behavior of resident mice; naloxone influenced not only intruder defensive behavior, but also other non-aggressive behaviors. The social role of the drug recipient and his prior history of aggressive behavior are important determinants of morphine and naloxone effects on aggression.

Aggression↗
PubMed1985

Social status as determinant of alcohol effects on aggressive behavior in squirrel monkeys (Saimiri sciureus).

We investigated the behavioral effects of alcohol, especially those on aggression, on members of established groups of squirrel monkeys. A continuous measurement of monkey behavior in groups revealed consistent differences between dominant and subordinate animals. Dominant monkeys aggressed more frequently than subordinate monkeys, and spent less time in stationary postures. Alcohol produced dose-related biphasic changes in the number of threats, grasps, and displacements exhibited by dominant but not subordinate monkeys. Low doses of alcohol (0.1, 0.3, 0.6 g/kg) increased the frequency of aggressive behavior, and high doses (1.0 g/kg) decreased these behaviors. The largest change in behavior was evident in the first 20-40 min after injection, with a return to baseline 60-120 min later. The aggression-enhancing effect of alcohol in dominant monkeys required a stable baseline, which was obtained by daily administration of distilled water. Low levels of aggressive and associative behavior in subordinate monkeys were relatively unaffected at any dose of alcohol. They were associated with and aggressed against more often by untreated members of the group. The status-dependent effects of alcohol may be related to the neuroendocrine and neurotransmitter profiles characteristic of dominant and subordinate monkeys.

Aggression↗
PubMed1985

Naloxone injections into the periaqueductal grey area and arcuate nucleus block analgesia in defeated mice.

In a situation of social conflict, mice that are defeated by an opponent exhibit a marked analgesia. Microinjections of naloxone (1 or 10 micrograms) into the periaqueductal grey area (PAG) or into the region of the arcuate nucleus prior to the defeat prevented the emergence of analgesia. Microinjections of morphine (5 micrograms) into these sites had previously been shown to produce profound analgesia. Mice whose adrenals were removed rapidly developed analgesia when attacked by a stimulus animal. Injection of naloxone into PAG also antagonized defeat-induced analgesia in adrenalectomized mice. These observations indicate that sites and processes in the brain rather than in the periphery are responsible for the development of analgesia in mice that are subjected to social defeat.

Analgesia↗
PubMed1985

Testosterone modulates the effects of ethanol on male mouse aggression.

In a series of three experiments, we evaluated the degree to which the effects of acutely administered ethanol on aggressive behavior of male CFW mice toward a male intruder interact with, and depend on, androgen levels. In the first experiment, mice were tested at 15 min after 0, 0.1, 0.3, 1.0, 1.7, or 3.0 g/kg of ethanol PO. The highest dose (3.0 g/kg) significantly suppressed aggression by the male residents. In the second experiment, aggressive behavior was suppressed from 5 to 60 min after 3.0 g/kg ethanol administration PO. The third experiment evaluated the role of testosterone in these effects in another set of male mice that were castrated and then implanted with a 7.5-mm or 2.5-mm silastic capsule of testosterone (T) or a silastic capsule containing cholesterol as a control. The castrated mice with 2.5-mm T capsules or cholesterol capsules had lower baseline levels of aggression than intact mice or castrated males with 7.5-mm T capsules, but they demonstrated an alcohol dose-response pattern similar to that of the intact males. The castrated males with 7.5-mm T capsules had a different dose-response curve than the other males. Doses of 1.0 and 1.7 g/kg ethanol PO significantly enhanced aggression; 5.6 g/kg was required to suppress aggression. Ethanol effects on aggressive behavior did not require T or changes in T level, but T levels altered behavioral sensitivity to ethanol.

Aggression↗
PubMed1984

Aggression persists after ovariectomy in female rats.

Aggression occurs not only in males but also in females, however, under different sex-specific stimulus and endocrine conditions. After being housed with males, female rats exhibit frequent and intense aggressive behavior toward unfamiliar rats. However, the female residents primarily attack female intruder rats, while the male residents attack males and not females. Altering the hormonal condition of the intruders can modify the behavior that they provoke from the residents. Castration of the male intruders reduces aggression from male residents, but ovariectomy of the female intruders does not alter the behavior of the female residents. Treatment of the gonadectomized intruders with gonadal steroids significantly alters the response of the male residents. Resident-intruder aggressive behavior depends on the presence of the testes in the male residents but not on the ovaries or on lactation in the female residents. Even 7 weeks after ovariectomy the female residents continue to show aggressive behavior toward female intruders. In the same time period the castrated male residents show a marked decrease in aggressive and sexual behavior.

Aggression↗
PubMed1984

Heightened aggressive behavior by animals interacting with alcohol-treated conspecifics: studies with mice, rats and squirrel monkeys.

Drug-free mice, rats and squirrel monkeys showed more aggression toward alcohol-treated conspecifics than under control conditions. Quantitative ethological analysis was used to assess the dose-dependent effects of ethyl alcohol on a range of aggressive, submissive, defensive, escape responses as well as on non-agonistic behavior such as associative responses, grooming, and locomotor activities. Two experimental situations were studied: resident-intruder confrontations in mice and rats, and interactions between members of established groups of squirrel monkeys. After PO administration of ethyl alcohol to intruder mice and rats, the non-drugged resident mice and rats attacked, threatened, and pursued intruders at higher frequencies during 5-min encounters. Similarly, subordinate squirrel monkeys who were members of three established groups, when given alcohol, were grasped, displaced, and displayed to more frequently by non-drugged group members than after water control injections during the first 40 min after injection. This change in aggressive behavior by non-drugged animals was related to the alcohol dose given to the intruder or subordinate animal; near-ataxic alcohol doses (3.0 g/kg in mice, 1.7 g/kg in rats, 1.0 g/kg in squirrel monkeys) altered the behavior of animals whose prevalent pattern is defensive and submissive so that they were the subject of most frequent and intense aggression.

Aggression↗
PubMed1983

d-Amphetamine in squirrel monkeys of different social status: effects on social and agonistic behavior, locomotion, and stereotypies.

The influences of social status on amphetamine-induced behavioral effects in squirrel monkeys were investigated. Social status was determined by constructing a sociogram. d-Amphetamine (0.3--1.0 mg/kg orally, 0.3 and 0.6 mg/kg IM) increased stereotyped head movements and reduced the time spent in the sitting posture in all monkeys (N = 25) regardless of sex, age, or social status. The high levels of locomotor activity in dominant and juvenile monkeys were decreased at higher amphetamine doses (0.6 mg/kg IM, 0.6 and 1.0 mg/kg orally), whereas the same doses increased locomotion in otherwise less active subdominant and submissive animals. Low doses of amphetamine (0.1, 0.3 mg/kg) decreased the incidence of agonistic behavior initiated by dominant monkeys, and higher doses (0.6, 1.0 mg/kg) caused these monkeys to change from predominant initiators of agonistic behavior into recipients. At 2 h after amphetamine administration (0.3 mg/kg IM), the high levels of locomotor behavior had returned to baseline, the social isolation began to disappear, and the disrupted agonistic behavior of dominant monkeys returned to control levels, yet the stereotyped head movements continued to occur with high frequency. In half of the monkeys, amphetamine produced a large increase in distress-like vocalizations. Amphetamine-mediated motor stereotypies may be mediated by mechanisms different than those responsible for agonistic behavior. The selective changes in agonistic behavior by dominant monkeys when challenged with amphetamine may reflect a status-related functional alteration of catecholaminergic processes upon which the drug acts.

Agonistic Behavior↗
PubMed1983

Habituation of aggression in mice: pharmacological evidence of catecholaminergic and serotonergic mediation.

A pharmacological study was undertaken to evaluate the role of catecholamines and serotonin in the mediation of aggression. The dose-effect relationship of d-amphetamine, apomorphine, methysergide, lisuride, and the time-dependent effects of 10 mg/kg p-chloroamphetamine (PCA) were determined on aggressive behavior in a habituation paradigm. The frequency of attacks and sideways threats exponentially declined in ten consecutive confrontations between resident and intruder mice, and recovered when a new intruder was introduced. d-Amphetamine (0.1-5.0 mg/kg) and apomorphine (0.03-1.0 mg/kg), administered IP 5 min before the first confrontation, attenuated the usual decline of attack and threat in subsequent trials. PCA enhanced attack, sideways threat, and locomotion at day 1 after injection. Methysergide (1, 3, 10 mg/kg) and lisuride (0.03, 0.3, 1.0 mg/kg) suppressed all activity, including locomotion and aggression. The data support the hypothesis that catecholamines mediate the activation of aggression, but do not indicate an inhibitory role for serotonin. Aggression in the resident-intruder paradigm appears to require intact serotonin activity.

Aggression↗
PubMed1983

Ethological analysis of drug action on aggression and defense.

Psychopharmacological research on aggression pursues divergent objectives: From a pharmacological perspectives, animal aggression tests are employed in order to differentiate classes of psychotherapeutic drugs and to screen for specific agents. Psychiatric interests in animal aggression research attempt to model pathological aggressive behavior in humans. These efforts have yielded disappointing results because they are based neither on a detailed understanding of the behavioral characteristics of aggression nor of the relevant neural processes. The ethological approach to aggression research focuses on biologically relevant situations and behavior patterns. Quantitative methods describe drug action on the interactive and episodic nature of aggressive behavior. An analysis of the temporal pattern of aggressive behavior indicates how, for example, amphetamine and alcohol modulate sequences of aggressive interactions.

Aggression↗
PubMed1982

Opioid-like analgesia in defeated mice.

Mice exposed to repeated attacks by other mice showed decreased nociception in response to radiant heat focused on their tails. This form of analgesia was blocked by centrally acting opiate antagonists and was not observed in morphine-tolerant mice; furthermore, mice repeatedly subjected to defeat. Mice of the CXBK strain, which respond weakly to morphine, displayed only moderate analgesia following defeat. These findings suggest that endogenous opioid-mediated analgesic mechanisms are readily activated by situations involving biologically significant forms of stress, such as defeat.

Aggression↗
PubMed1982

Disruption of primate social behavior by d-amphetamine and cocaine: differential antagonism by antipsychotics.

Psychostimulants lead to withdrawal from social interactions and to a decline of affective behavior in squirrel monkeys. These changes, in addition to motor stereotypies, may be related to stimulant-induced psychosis in humans. In the first of two series of experiments, 1 mg/kg d-amphetamine or 10 mg/kg cocaine, administered orally three times over 24 h to one adult male member of an established group (n = 6-9), engendered stereotyped movements of the head and hands, reduced rest postures, and greatly reduced all forms of social initiatives. Chlorpromazine (0.25-1.0 mg/kg), haloperidol (0.25, 0.5 mg/kg), and physostigmine (0.04, 0.08 mg/kg), administered before the third amphetamine or cocaine injection, blocked the motor stereotypies and hyperactivity. Chlorpromazine, haloperidol, and physostigmine did not reliably antagonize the pronounced reduction in social behavior. The second series of experiments focused on agonistic behavior in the context of resident-intruder confrontations and on affiliative behavior toward group members. d-Amphetamine (3 X 0.5 mg/kg) and, to a lesser extent, cocaine (3 X 10 mg/kg) decreased affiliative and agonistic behavior. Chlorpromazine (0.5, 1.0 mg/kg) and haloperidol (0.1, 0.25 mg/kg) did not block the severe disruption of the affiliative and agonistic behavior in amphetamine-treated monkeys; physostigmine (0.06 mg/kg) reversed the decline in time spent close to the familiar monkey in amphetamine-treated monkeys. By contrast, stimulant-induced stereotypies were effectively antagonized by chlorpromazine, haloperidol, and physostigmine. These results suggest that psychostimulant-induced changes in primate social behavior may be mediated by mechanisms other than those underlying motor stereotypies.

Animals↗
PubMed1982

Effects of phencyclidine on aggressive behavior in mice.

The effects of phencyclidine on aggressive behavior in mice and the possible mechanism of action for these effects were examined. PCP at a dose of 10.0 mg/kg significantly decreased the number of attacks by resident mice toward intruders. Significant increases in the number of attacks by non-drugged residents toward the intruders who were given high doses of PCP (6.0 and 10.0 mg/kg) were observed. Only the higher doses of PCP (6.0 and 10.0 mg/kg) significantly increased the duration of locomotion. The increase in locomotion was dependent upon the time after administration of the drug. Hyperactivity was present at 30 minutes for both doses and hypoactivity was present at three hours after administration of 3.0 mg/kg. PCP did not significantly alter the frequency of attacks in an unfamiliar test locale. Pretreatment with haloperidol (1 mg/kg) partially blocked the PCP-induced hyperactivity but pretreatment with methysergide (3 mg/kg) did not. Neither haloperidol nor methysergide blocked the suppressive effects of PCP on aggressive behavior. It is concluded that PCP does not increase aggressive behavior in mice but high doses will decrease aggression. PCP-treated intruder animals provoke more aggression by non-drugged animals. PCP-induced hyperactivity appears to be mediated by dopaminergic systems.

Aggression↗