Biomedical subjects

K A Miczek

Publications and source records attributed to K A Miczek.

At least 91 records · Page 5Linked to original sources

PubMed1992

Heightened aggressive behavior during morphine withdrawal: effects of d-amphetamine.

The morphine withdrawal syndrome is composed of profound short- and long-term changes in autonomic, somato-motor and affective functions. In mice, morphine withdrawal produces heightened aggressive behavior and alterations in motor behavior; however, it is unclear whether these changes in behavior occur in unison and are dependent on a common mechanism or occur independently. In order to characterize the morphine withdrawal syndrome in mice, male Swiss-Webster mice were housed with female partners for 3-4 weeks before being implanted subcutaneously with morphine or placebo pellets. The pellets were removed 72 h after implantation and behavioral measurements were conducted 5, 48 and 96 h after pellet removal. During these tests, mice received d-amphetamine (0.3-10 mg/kg) or saline after which they were assessed for changes in motor behavior and for changes in aggressive behavior while confronting a group-housed male "intruder". In morphine-withdrawn mice, frequency of attack behavior was increased by approximately 30% and this effect persisted for at least 4 days. In contrast, explosive jumping was increased and walking and rearing were greatly decreased at the onset of the withdrawal period but declined within the first 24 h and returned to control levels within 48 h of pellet removal. d-Amphetamine maintained the elevated level of aggressive behavior and sharply increased locomotion in morphine-withdrawn mice; in placebo-pelleted mice, d-amphetamine dose-dependently decreased aggressive behaviors while increasing locomotion. The differential time course and the differential modification by d-amphetamine suggest that heightened aggressive behavior is a long-lasting consequence of morphine-withdrawal based on separate mechanisms than the short-lived alterations in motor activity.

Aggression↗

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↗

PubMed1992

Morphine withdrawal aggression: modification with D1 and D2 receptor agonists.

Morphine withdrawal increases aggressive behaviors, induces explosive motor behaviors, and disrupts homeostatic functions in mice and rats. While many of these effects appear to result from altered dopaminergic activity during morphine withdrawal, the relative contributions of the D1 and D2 receptor subtypes remain unclear. In the present experiments, the D1 agonist SKF 38393 and the D2 agonist quinpirole were administered to male "resident" Swiss-Webster mice 5 h after the removal of a subcutaneously-implanted morphine or placebo pellet. These mice were then observed alone to determine changes in various motor activities and in confrontation with a group-housed male "intruder" to assess changes in aggressive behaviors. SKF 38393 decreased the display of aggressive behaviors by placebo and morphine-withdrawn mice without consistently altering walking or rearing. Quinpirole greatly decreased the display of aggressive behaviors by placebo mice and decreased aggressive behaviors in morphine-withdrawn mice to a lesser degree. The inhibitory effects of quinpirole were not specific to aggressive behaviors; low quinpirole doses also decreased the display of walking and rearing. In mice which received a low dose of SKF 38393 preceding quinpirole injection, pretreatment with the D1 agonist did not alter the effects of the D2 agonist quinpirole on motor activities but maintained high levels of aggression in morphine-withdrawn mice. The differential modification of aggressive and motor behaviors by selective dopaminergic agonists during morphine withdrawal further supports the suggestion that aggressive and motor behaviors are controlled independently; furthermore, D1 receptor stimulation appears to have particular relevance for the display of aggressive behaviors during morphine withdrawal.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1992

Increased GABAA-dependent chloride uptake in mice selectively bred for low aggressive behavior.

Selective breeding for aggressive behavior alters GABA-dependent chloride uptake and behavioral response to benzodiazepine treatment. Pharmacological and biochemical studies examined subjects from three lines of adult male ICR mice selectively bred for either high levels or low levels of aggressive behavior, as well as unselected controls. Selective breeding produced two lines of behaviorally distinct males. During 5-min dyadic confrontations with an outbred stimulus animal, untreated low-aggressive mice spent more time in walking, rearing, and social interaction than untreated high-aggressive mice. The three lines also showed different responsiveness to the aggression increasing and decreasing effects as well as the sedative effects of benzodiazepine treatment. High doses of chlordiazepoxide (17, 30 mg/kg) reduced motor behaviors (walk, rear and groom) in the low-aggressive line without altering these behaviors in the high aggressive line. In the high-aggressive line, the same doses of chlordiazepoxide (17, 30 mg/kg) produced a behavioral shift; aggressive behaviors were reduced while social behaviors increased to levels similar to the untreated low-aggressive line. In contrast, only the unselected line pursued and threatened more after a low dose of chlordiazepoxide (3 mg/kg). The three lines also showed alterations at the GABAA-benzodiazepine receptor complex. Specific uptake of [3H]Ro-15-1788 was increased in cerebral cortex, hypothalamus and hippocampus in the low-aggressive line, and was reduced in these areas in high-aggressive line when compared with unselected controls. Similarly, GABA-dependent chloride uptake in cortical synaptoneurosomes was augmented in low-aggressive mice and decreased in high-aggressive mice when compared to unselected controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

PubMed1991

Tolerance to the analgesic, but not discriminative stimulus effects of morphine after brief social defeat in rats.

One of the most prominent consequences of defeat in a social confrontation is a long-lasting tolerance-like insensitivity to the analgesic effects of opiates, even when only small short-lived changes in nociception are detectable during the acute social stress. The present experiments examined (1) which kinds of social experiences lead to morphine tolerance, (2) whether or not the morphine tolerance in defeat-experienced rats extends from the analgesic effects to the discriminative stimulus and rate-decreasing effects of morphine, and (3) how long morphine tolerance lasts after a defeat experience. After five brief social confrontations including attack and threat by a resident rat leading to submission or defeat of the intruder, the latter exhibits marked tolerance to the analgesic effects of morphine, but not to the discriminative stimulus or behaviorally suppressive effects. Changes in social housing did not alter morphine's behavioral effects. Tolerance to the analgesic morphine effects was detected for 2 months after the defeat experience, whereas the discriminative stimulus and rate-decreasing effects were closely similar to those before defeat. This pattern was seen in animals for whom discriminative stimulus training with morphine was suspended after defeat as well as in those for whom it continued. In additional defeated and non-defeated animals, morphine's effects on the acoustic startle reflex was assessed. In contrast to the tail flick reflex to a noxious heat stimulus, the acoustic startle response remained unaffected by defeat experience or by morphine (up to 30 mg/kg). The long-lasting and large degree of tolerance after brief social defeat experiences appears to be limited to the analgesic effects of morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1991

Ultrasounds during morphine withdrawal in rats.

Ultrasounds (US) in rats may communicate affective states, as they occur only in highly significant situations such as maternal care, sex and aggression. Withdrawal from morphine is a manipulation which dramatically alters autonomic, somatic and motor functions; the present experiment demonstrated the production of US in this context and the influence of previous social experience in their production. Sixty male Long-Evans rats with distinct social experiences (social inexperience, defeat or copulation) underwent 72 h of continuous morphine exposure (4 x 75 mg morphine or placebo pellets) and subsequent withdrawal. The rats were observed for 10 min in equally treated pairs and while solitary at 6, 24 and 96 h after pellet removal. US were emitted by all groups and consisted primarily of two distributions of pure tone whistles with little frequency modulation: 1-2 s 21-25 kHz ("low") signals and the more prevalent 0.02-0.1 s 44-52 kHz ("high") signals. Morphine withdrawn rats lost weight, displayed wet dog shakes, were hypoactive and emitted threefold more US vocalizations with a fourfold greater duration than placebo controls. Defeat-experienced morphine withdrawn rats were more hypoactive than either socially inexperienced or copulatory experienced rats while increasing vocalization rates and total duration. This increased duration of ultrasounds included a shift in the distribution of individual US durations from less than 0.3 s to greater than 1.0 s. US are readily emitted at high rates in morphine withdrawn laboratory rats, which may implicate an opioid involvement in their generation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

PubMed1991

Ethopharmacological studies of anxiolytics and aggression.

This paper presents examples of the application of ethopharmacology to the study of aggression. Low doses of benzodiazepines may increase aggression under appropriate conditions. In various animal models in male and female rats and mice the aggression enhancing effects are particularly marked when aggression is inhibited by internal or external events. It is therefore suggested that benzodiazepines have no direct effect on aggression, but modulate inhibitory factors which regulate aggression.

Aggression↗

PubMed1990

Sexual differentiation and the effects of alcohol on aggressive behavior in mice.

Male and female mice are differentially sensitive to the effects of alcohol on aggressive behavior. We investigated the role of testosterone during sexual differentiation in determining sex differences in alcohol effects on aggression. On the day of birth male mice were castrated or sham-operated. Neonatal female mice were injected with 250 micrograms of testosterone propionate (TP) or the oil vehicle. At approximately 75 days of age the mice which had not been gonadectomized at birth were gonadectomized. Control males and androgenized female mice then received 7.5 mm Silastic capsules containing testosterone, SC. Aggressive behavior toward an intruder was assessed following administration of ethanol (0.1-3.0 g/kg) or water, PO. Neonatally sham-gonadectomized male mice had a significant increase in aggressive behavior following administration of 1.0 g/kg alcohol, with no significant suppression of aggression at 3.0 g/kg. Neonatally androgenized female mice showed neither the male-typical response to adult testosterone and alcohol, nor did they show the female-typical response. Neonatally gonadectomized males showed an alcohol dose response curve that was similar to that of androgenized females. Postnatal testosterone did not appear to completely determine the male- and female-typical responses to alcohol on aggression. The critical period for this sexually dimorphic response to alcohol and testosterone may be primarily prenatal.

Aggression↗

PubMed1990

Opiate antagonists enhance the working memory of rats in the radial maze.

Two experiments tested the influence of the opiate antagonists naloxone and naltrexone on the spatial working memory of rats in a 12-arm radial maze. In Experiment 1, ten rats were serially forced to visit six randomly selected arms, then were removed from the maze for delays of either 30, 60, or 240 minutes, and then returned to the maze for a free-choice memory test with all 12 arms available. Five minutes into the delay, rats were injected intraperitoneally (IP) with either physiological saline or naloxone (1 mg/kg). When injected with naloxone the rats revisited forced-choice arms less often than when injected with saline during a subsequent free-choice test. In Experiment 2, twelve rats showed a similar facilitation of working memory when injected with the opiate antagonists naltrexone (0.3 mg/kg) and naloxone (1 mg/kg) in comparison to a saline control condition. These findings demonstrate the beneficial effects that opiate antagonists exert on working memory-based performance in the radial maze. They may also resolve conflicting reports about the influence of opiate antagonists on radial maze performance, by suggesting that the choice of measurement and testing conditions are crucial for detecting these effects in working memory procedures.

Animals↗

PubMed1989

Morphine effects on maternal aggression, pup care and analgesia in mice.

In order to assess the respective contribution of opioid receptors to the behavioral and physiological characteristics of lactating animals, we challenged mice with morphine at different phases of the lactation period. Sensitivity to morphine's effects on aggressive behavior, pup care, pain response and body temperature were measured. Lactating mice were assigned to 1 of the 3 weeks of lactation and to 1 of 5 doses of morphine sulfate (0, 1, 3, 6, 10 mg/kg IP). After morphine administration, rectal temperature and tail flick were assessed. Behavior towards three pups was observed for 5 min, followed by an aggression test with a female intruder. Morphine significantly increased the latency to retrieve pups and decreased aggressive behavior at doses that do not decrease motoric activity. Compared to virgin mice, lactating females are less sensitive to the analgesic actions of morphine but similarly sensitive to its hypothermic properties. The fact that virgin and lactating females can be distinguished on the basis of their sensitivity to morphine-induced analgesia suggests that lactating animals undergo functionally relevant changes in opioid regulation of pain sensitivity. Furthermore, morphine's specific and potent inhibition of pup retrieval supports the hypothesis that decreased opioid peptide activity is important for the expression of certain postpartum behaviors.

Aggression↗

PubMed1989

Temporal patterning of ultrasonic distress calls in the adult rat: effects of morphine and benzodiazepines.

Opioids and benzodiazepines modulate the ultrasounds that rats emit before being presented with aversive stimulation. Mild, intermittent 10 s electrical tail stimulation induces rats to emit 20-30 kHz ultrasounds before and after the stimulation. Analysis of the temporal parameters of the sounds via a customized computer system reveals them to be emitted in bouts of about five sounds, each sound being separated from the next by 0.2-0.35 s pauses. Morphine decreases the per cent time vocalizing during the pre-stimulation period, with 6 mg/kg being fully suppressive. This effect is reversed by 1 mg/kg naloxone pre-treatment. Chlordiazepoxide and morphine have opposite effects on the temporal structure of the pre-stimulation calls; chlordiazepoxide induces longer bouts with more pulses, and morphine dissolves the bout structure into a series of single pulses. These differential and selective effects of morphine and benzodiazepines on the occurrence and temporal structure of ultrasounds may be relevant to characteristics of different affective expressions.

Animals↗

PubMed1989

Temporal and sequential patterns of agonistic behavior: effects of alcohol, anxiolytics and psychomotor stimulants.

Social and agonistic interactions are composed of a range of species-typical acts, postures, displays and other communicative signals that follow characteristic patterns. Descriptive and analytic methods permit an assessment of the temporal and sequential features of highly probable patterns of agonistic interactions. Analysis of the intervals that separate consecutive attacks by a resident mouse or rat toward an intruder identifies bursts or epochs of attacks. Amphetamine (1.25, 2.5 mg/kg), but not diazepam or alcohol, alters the burst pattern of attack behavior. Higher doses of alcohol, but not diazepam, in either resident male rats or in lactating rats confronting an intruder, reduce the sequences of aggressive acts and postures with high transition probabilities as identified by lag sequential analysis. These results suggest that temporal and sequential patterning mechanisms may be differentially altered by amphetamine- and alcohol-type substances. These neural for many types of behavior.

Aggression↗

PubMed1989

Brain 5-HT and inhibition of aggressive behavior in animals: 5-HIAA and receptor subtypes.

Evolutionary constant serotonin (5-HT) neuronal systems evolved along medial brain structures; yet, wide variations in functionality characterize serotonergic systems in mediating aggressive responses in species ranging from lobsters, ants, electric fish, and rodents to primates. So far, the attempts to correlate cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) levels with measures of aggression have revealed inverse, direct, or no correlations in different nonhuman primate species. It is difficult to harmonize the occasional correlations between CSF 5-HIAA and adaptive aggressive acts in nonhuman primates (a) with clinically diagnosed suicidal or impulsive individuals, and (b) with the biochemical, anatomical, and presumably functional differentiation of 5-HT pathways and receptor subtypes. Eltoprazine, a mixed 5-HT1A/B agonist, and meta-trifluoro-methylphenyl-piperazine HCl (TFMPP), a more selective 5-HT1B agonist, specifically decrease aggressive behavior in several animal species and situations in both sexes without detriment to other social, exploratory, or motoric activities. A definite role for 5-HT1A, 5-HT2, and 5-HT3 receptor subtypes in the mechanisms mediating aggressive behaviors has to await the development of selective agonists and antagonists, respectively.

Aggression↗

PubMed1989

Amphetamines: aggressive and social behavior.

Clinical case reports and survey data point to incidences of intense violence in certain individuals self-administering high doses of amphetamine via the intravenous route. It is unclear how common this amphetamine effect is, what circumstances promote its occurrence, and which characteristics predispose an individual to exhibit this effect. Amphetamine may engender a dose-dependent biphasic effect on aggressive behavior in experimental situations, both with human and animal subjects, as, for example, in subjects that have habituated to an aggression-provoking stimulus. Most often, however, amphetamines disrupt social, sexual, maternal, and aggressive behavior patterns in a dose-dependent manner; neither tolerance nor sensitization appears to develop to these disruptive effects. Amphetamine consistently enhances defensive and flight reactions in various experimental situations and animal species. This effect appears to be mediated by brain dopaminergic systems. So far, no dopaminergic, noradrenergic, or opioid antagonists have been found that attenuate, reverse, or prevent the disruptive effects of amphetamines on social and aggressive behavior. The evidence from opioid-withdrawn subjects strongly suggests a profound modulatory influence by opioid peptides on the aggression-altering effects of amphetamines.

Aggression↗

PubMed1988

Effects of alcohol on aggressive behavior in squirrel monkeys: influence of testosterone and social context.

Social status and reproductive cycle determine the effects of acute, low doses of alcohol on the social behavior of squirrel monkeys. Alcohol produces biphasic effects on the behavior of dominant but not subordinate monkeys, and only during the mating season. The change in alcohol sensitivity measured in dominant monkeys coincides with changes in plasma testosterone levels. In order to directly study the interaction between alcohol, testosterone and aggressive behavior, testosterone propionate (TP, 25 mg/kg/day, SC) was administered to either dominant or subordinate male monkeys belonging to four separate groups, resulting in significantly elevated plasma levels of testosterone (i.e., 905 +/- 43 ng/ml in subordinates; 171 +/- 19 ng/ml in dominants). Two to three weeks after the beginning of testosterone treatment, the monkeys were administered doses of alcohol (0.1-1.0 g/kg). The behavior of subordinate monkeys was unaffected by TP treatment (even after the dominant monkey from each colony was removed and housed separately for 6 weeks). Testosterone treatment altered the sensitivity of subordinate monkeys to alcohol. Low doses of alcohol increased the frequency of threats, grasps, and displacements exhibited by subordinate monkeys with exogenously elevated testosterone. Daily administration of TP to dominant monkeys during the non-mating season did not affect the behavior of the treated animals in the group, although the body weight of TP-treated monkeys was similar to that measured during the mating season. Low doses of alcohol increased the frequency of threats, grasps, and displacements in dominant monkeys maintained on TP. We also tested the role of social context in maintaining high levels of plasma testosterone, and alcohol sensitivity in dominant monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

PubMed1988

Androgen dependency of alcohol effects on aggressive behavior: a seasonal rhythm in high-ranking squirrel monkeys.

The relationship between testosterone and alcohol's effects on social behavior within established groups of squirrel monkeys was studied. Consistent behavioral differences between dominant and subordinate monkeys were quantitatively measured using computer assisted, continuous measurement techniques. Blood samples collected during the mating season revealed plasma testosterone measures of 202.9 +/- 13.4 ng/ml in dominant monkeys and 28 +/- 6.2 ng/ml in subordinate monkeys. Alcohol (0.1-1.0 g/kg, PO) produced a dose-related decrease of testosterone levels in dominant monkeys. Concurrently, alcohol produced biphasic effects on the behavior of dominant but not subordinate monkeys; low doses (0.1, 0.3 g/kg) increased the frequency of threats, grasps, and displacements. Subordinate monkeys were not affected at any dose. During the non-mating season, plasma levels of testosterone fell to 55.2 +/- 23.7 ng/ml in dominant monkeys and 7.3 +/- 1.7 ng/ml in subordinate monkeys. Plasma testosterone and the social behavior of both dominant and subordinate monkeys were unaffected by alcohol. These findings provide further evidence of a specific association between alcohol, testosterone and aggression in the non-human primate. High levels of testosterone that are evident during the mating season of dominant, male squirrel monkeys may activate alcohol sensitive brain substrates of aggressive behavior.

Aggression↗

PubMed1988

Social, motor, and autonomic signs of morphine withdrawal: differential sensitivities to catecholaminergic drugs in mice.

Drugs that predominantly influence catecholamines were used in order to simultaneously determine their ability to alter salient signs of social, motor and autonomic activity during morphine withdrawal, and to compare the sensitivity of each of these signs to these drugs. Cocaine, d-amphetamine, apomorphine and L-dopa increased attack and threat, but did not induce defensive behavior in morphine-withdrawn resident mice who were more responsive to the aggression-enhancing effects of these drugs than placebo control mice. Concurrently measured withdrawal jumping was not affected by these drugs, and the sensitivity to the hypothermic effects of these drugs was reduced. In contrast, clonidine decreased attack and threat behaviors, and morphine-withdrawn mice were more sensitive to this inhibitory influence. But like the stimulant drugs, clonidine did not affect withdrawal jumping, and the hypothermic action of clonidine was attenuated in morphine-withdrawn mice. These findings show that in mice, opiate withdrawal leads to altered attack and threat that is further amplified by catecholaminergic drugs. The present pattern of results indicates differential drug effects on social, motor and autonomic functions when the behaviors are measured 48 h following withdrawal.

Animals↗

PubMed1988

Naltrexone blocks amphetamine-induced hyperactivity, but not disruption of social and agonistic behavior in mice and squirrel monkeys.

Significant anatomical overlap of opioid and dopamine receptors as well as reciprocity of control over synthesis, metabolism, and release of opioid peptides and dopamine in brain suggests functional interactions between the two systems. In the first of two studies, the behavioral effects of amphetamine and naltrexone alone, and in combination were studied in established groups of socially interacting squirrel monkeys. Naltrexone (0.1-10.0 mg/kg, IM) increased locomotion and marking behavior in subordinate monkeys. The frequency of social initiatives directed at treated subordinate monkeys by untreated members of the group was also increased. The behavior of dominant monkeys was relatively unaffected, except at the highest dose when autonomic distress was also evident. The frequency of walking bouts by both dominant and subordinate monkeys was increased by amphetamine (0.1-0.6 mg/kg, IM), and the social behavior of dominant monkeys was disrupted by drug treatment. Naltrexone (0.1 mg/kg, IM) significantly antagonized amphetamine's effects on motor behavior, and enhanced or did not affect amphetamine's effects on social behavior. In a second study, the interaction of amphetamine (0.63-10.0 mg/kg, IP) and naltrexone (0.1-10.0 mg/kg, IP) on the behavior of resident male mice during confrontations with a male intruder was studied. Naltrexone selectively reduced the frequency of attack at the highest dose tested. Amphetamine increased locomotor activity and decreased attack and threat behavior in resident mice. A low dose of naltrexone (1.0 mg/kg, IP) blocked amphetamine's effects on locomotion and enhanced the disruption of aggressive behavior. The amphetamine-naltrexone interaction on locomotor activity in mice and monkeys is consistent with opioid receptor modulation of dopamine mediated functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗