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Suppression of cocaine- and food-maintained behavior by the D2-like receptor partial agonist terguride in squirrel monkeys.

RATIONALE: The D2-like receptor partial agonist terguride has a profile of behavioral effects in rats that suggests potential benefit as a pharmacotherapy for cocaine addiction. OBJECTIVES: The present study investigated the effects of terguride on cocaine- and food-maintained behavior in squirrel monkeys. METHODS: Squirrel monkeys were trained to respond on a second-order schedule (FI 10 min, FR 10 or 30:S) of either i.v. cocaine injection or food pellet delivery. Additional monkeys were studied using quantitative observational techniques to construct side effect profiles. Under each procedure, the effects of terguride were compared with those of the reference D2-like receptor antagonist nemonapride and the D2-like receptor full agonist quinpirole. RESULTS: Terguride and nemonapride, but not quinpirole, dose-dependently reduced cocaine-maintained behavior. In animals self-administering food, terguride decreased response rates at doses lower than those required to suppress cocaine-maintained behavior. Effective doses of terguride had no systematic effect on motor activity or muscle rigidity, whereas effective doses of nemonapride virtually eliminated motor activity and induced severe catalepsy. The primary observable effects of terguride were a modest increase in self-directed behavior (a D2-receptor agonist-like effect) at intermediate doses and a small increase in static posture (a D2-receptor antagonist-like effect) at the highest dose tested. CONCLUSIONS: The results suggest that terguride has advantages over conventional D2-like receptor antagonists and agonists as a candidate pharmacotherapy for cocaine abuse; however, terguride significantly reduces food-maintained behavior at lower doses than those needed to decrease cocaine-maintained behavior suggesting limitations on the utility of terguride as a medication for cocaine addiction.

Animals↗

Castration in Gambel's and Scaled Quail: ornate plumage and dominance persist, but courtship and threat behaviors do not.

During the breeding season, testosterone in male birds is often linked to some secondary sexual ornaments, courtship behaviors, and intrasexual aggression. I examined the effect of castration on plumage expression in Gambel's Quail (Callipepla gambelii), a species in which males are highly ornate, and in Scaled Quail (C. squamata), an unornamented species. Using male pairs, each consisting of a castrate and a control, I also assessed whether castration affected (1) the behavior of males, (2) the mating decisions of females, or (3) the outcome of male-male competition. Castration did not alter the plumage of male Gambel's or Scaled Quail. In these species, and some other members of the avian order Galliformes, production of ornate plumage appears to be independent of testosterone. In contrast, castration reduced or eliminated courtship behaviors. Females almost never preferred castrated individuals. During male-male competition, castrates also exhibited lower rates of threat behaviors, which appear to be identical to those used during courtship. Castration did not, however, influence the outcome of male-male competition. Castrates of both species exhibited overt aggression (pecks, chases, displacement) and frequently won male contests. Such results suggest that certain types of aggressive behavior may be testosterone-independent. In both Gambel's and Scaled Quail, male body size correlated positively with dominant individuals.

Agonistic Behavior↗

Behavioral and neurochemical changes in rats simultaneously exposed to manganese and lead.

Groups of rats were exposed simultaneously to manganese chloride (3 mg Mn2+/ml water) through drinking water and lead acetate intraperitoneally at dosages of 5.0, 8.0 and 12.0 mgPb2+/kg daily for a period of 14 days. The magnitude of changes in the behavioral pattern, contents of biogenic amines and accumulation of lead in the brain of rats simultaneously exposed to the two metals was significantly greater than observed in rats after exposure to either of the metals alone. A definite dose-response relationship was, however, noticed only with the changes in the motoractivity, norepinephrine, 5-hydroxytryptamine levels and in the accumulation of lead in rats simultaneously exposed to manganese and lead. The lowering in the contents of norepinephrine after combined treatment was found to be related with the decrease in the motoractivity in the rats. The exact role of depression in the levels of dopamine and 5-hydroxytryptamine in inducing marked impairment in learning ability and increased aggressive behavior in rats after the combined exposure to manganese and lead could not be ascertained. The overall analysis of the data indicated that the simultaneous exposure to manganese and lead, particularly with highest dose of the latter, may produce serious derangements in the behavioral pattern and levels of biogenic amines in the brain of rats.

Agonistic Behavior↗

Social and hormonal influences on behavior of adult male, female, and pseudohermaphroditic rhesus monkeys.

We previously demonstrated that in a simple pair test situation the expression of adult male sexual behavior by rhesus monkeys depends on both prenatal (organizational) and adult (activational) androgen exposure. In the present study we used a more complex social situation (trio tests) to evaluate the behavior of males, females, and female pseudohermaphrodites. In these trio tests, the experimental subjects were tested with two estrogenized stimulus females simultaneously. Sex differences in behavior were made apparent by this complex testing situation that could not have emerged in the pair test. Gonadectomized males and female pseudohermaphrodites, but not ovariectomized females that were concurrently receiving TP, exhibited increased male sexual behavior in trio tests compared to pair tests. In trio tests, the males and pseudohermaphrodites showed evidence of partner preference by interacting almost exclusively with one of the two stimulus females. These "preferred females" in turn were responsible for the majority of the proceptive behavior exhibited in these tests. Ovariectomized females rarely displayed male sexual behavior in either test situation. These results further support the hypothesis that prenatal androgen exposure predisposes monkeys to exhibit masculine behavior traits when they reach adulthood and are exposed to the activational influences of androgens.

Agonistic Behavior↗

Anosmia and play fighting behavior in prepubescent male and female rats.

Prepubescent male and female rats were paired after intranasal treatment with isotonic zinc sulfate or saline solutions to determine the influence of peripheral anosmia upon play fighting behavior. In Experiment 1, male isolate residents pinned intruders significantly more often than intruders pinned residents but anosmia treatment had no influence on pinning behavior. In Experiment 2, males and females differed significantly in all major categories of play fighting but anosmia treatment had no influence on play fighting of either males or females. In Experiment 3, male groups matched for play fighting behavior prior to intranasal zinc or saline treatment were paired with like-treated males. All males in all pairings engaged in play behavior but anosmic males played less than controls. Evidently, intranasal zinc treatment depresses play behavior only when both members of a pair are anosmic. Play behavior is more markedly affected by resident-intruder status and by gender than by peripheral anosmia.

Aggression↗

Effects of water deprivation on urine marking and aggression in male house mice.

This study assessed the effects of water deprivation on male mouse urine marking and aggressive behaviors and endurance. In Experiment 1, the size of marks and frequency of marking were examined in 3 groups given 3 different weights of potato/day as their source of water. Males receiving the least water, 1.5 g potato/day, marked at significantly lower rates than males receiving 3 g potato/day or 6 g potato/day (p less than 0.01). The size of urine marks of males was judged by a panel to be unaffected by water deprivation. In Experiment 2, water-deprived males were not as aggressive as normal males and when paired with them were almost always subordinated. Experiment 3 tested the hypothesis that water-deprived males lost fights simply because they were weaker than normal males. When water-deprived and normal males were tested to determine the maximum length of time they could swim, no differences were found (p greater than 0.05). We conclude that water deprivation can directly affect the urine marking and aggressive behaviors of male mice. Such changes may be of adaptive importance during times of drought.

Aggression↗

Changes in aggressive behavior, thermoregulation, and endocrine responses in BALB/cLac and C57Bl/6J mice under cold exposure.

Effect of cold exposure on aggressive behavior, on the concentrations of testosterone and glucocorticoids, as well as on the oxygen consumption at different ambient temperatures, and calorigenic effect of noradrenaline have been studied in BALB/cLac and C57Bl/6J males. Under normal temperature conditions, there have been no significant interstrain differences. After cold exposure (5 weeks at 6-8 degrees C), C57Bl/6J mice exhibited more pronounced adaptive changes in thermoregulation and endocrine status (increase of glucocorticoids and decrease of testosterone concentrations were less expressed in C57Bl/6J than in BALB/cLac). At the same time, males of this strain demonstrated more intensive aggression than BALB/cLac mice. Some relations between physiological and behavioral changes caused by cold exposure are discussed.

11-Hydroxycorticosteroids↗

Sympathetic mediation of stress and aggressive competition: plasma catecholamines in free-living male tree lizards.

The sympathetic nervous system and adrenal catecholaminergic tissue act to prepare an animal for "fight or flight" by release of catecholamines into synapses and plasma. However, few studies have measured plasma catecholamines in nonmammalian vertebrates and none have measured them in free-living animals. We report plasma levels of norepinephrine (NE), epinephrine (EPI) and dopamine (DA) in free-living tree lizards (Urosaurus ornatus) bled in the field: 1) immediately after capture, 2) after 10 minutes of restraint, 3) immediately after a staged territorial encounter and 4) four minutes after the end of a staged territorial encounter. Time to capture and time to bleed after capture were also recorded for each sample. Time to capture had little effect on plasma catecholamines suggesting that plasma catecholamines do not rise during the brief pursuit by the investigator necessary to capture the lizards in the field. In contrast, plasma NE and EPI increased during blood collection. However, this response was very consistent allowing comparisons to be made using analysis of covariance to control for time to bleed. Results indicate that restraint stress caused a large increase in plasma levels of NE, E and DA. Plasma levels of NE and E, but not plasma DA, were also significantly elevated both immediately and 4 minutes after aggressive encounters, although less so than following restraint stress. These studies show that stress and aggression activate the sympatho-adrenal system. This activation could be involved in behavioral changes during aggression, meeting metabolic demands of the encounter, or both.

Adrenal Glands↗

Effects of repeated experience of aggression on the aggressive motivation and development of anxiety in male mice.

The sensory contact model allowed aggressive behavior to be formed in male mice as a result of repeated experience of victory in daily social confrontations. In individuals of the low aggressivity, high emotionality line CBA/Lac, repeated experience of aggression led to the development of anxiety, assessed in the elevated cross maze test. Males showed increases in aggressive motivation, measured in terms of increases in behavioral reactions to conspecifics in the partition test. It is concluded that repeated experience of aggression provokes the development of anxiety in male mice and that the level of developing anxiety, like its behavioral correlates, depends on the duration of aggressive experience and the mouse line studied.

Aggression↗

Familiarity with conspecific odor and isolation-induced aggressive behavior in male mice (Mus domesticus).

Male Swiss CD-1 mice (Mus domesticus, n = 60) were isolated for 24 days. In the isolation group mice were exposed to their own odor; in the familiarity group mice were familiarized with pairmates' odor by daily exchange of bedding; and in the unfamiliarity group subjects (exposed) were familiarized with pairmates' odor, whereas the pairmates (nonexposed) were familiarized with odors of other isolated mice. Aggressive behavior was scored during 20-min sessions. Familiarity with the pairmate's odor (familiarity and exposed subgroups) caused an enhancement of aggressive behavior, shown by the highest frequency of tail rattling and offensive upright posture and by a decrease in latency to the 1st attack. Nonexposed subjects showed high values of submissive upright posture, screaming, fleeing, and freezing. The results suggest that dominantlike behavior, acquired in social isolation, may be directed toward a conspecific whose odor is familiar.

Aggression↗

Instituting a disruptive conduct policy for medical staff.

A healthy work environment is one that promotes interaction and communication among all professionals, a positive and strong working relationship between the nurse manager and physician director, and activities such as joint patient care rounds, shared clinical protocols, and joint teaching of physicians and nurses. There are situations when a physician's unacceptable conduct leads to a disruptive environment for patients, staff, and fellow physicians. This article describes the steps taken in one institution to establish structures and systems to communicate behaviors that are unacceptable and a policy to be followed should disruptive behavior be encountered. Having systems and structures in place assists in promoting a healthy work environment.

Agonistic Behavior↗

[Different behavioral acts induced naturally or by electric stimulation of the brain].

A comparison was made between the reinforcing properties of a purposive attack provoked by stimulation of the hypothalamus and those of natural behaviour based on a certain motivation and exteroceptive stimuli. A model of an experiment with two cats has been evolved which made it possible to study simultaneously their behaviour in response to one and the same indifferent stimulus, reinforced in one cat by stimulation of the hypothalamus, while for the other, the stimulus acted as a signal of the attack on the part of the stimulated cat. It was shown that conditioned reflexes were not elaborated on the basis of reinforcement of the indifferent stimulus with behavioral effects of the purposive attack, produced by stimulation of the hypothalamus. It is assumed that conditioned reproduction of the purposive attack is impossible due to the absence of natural motivation; hence behavioral acts imposed by stimulation of the brain are not fixed in the memory.

Aggression↗

Neuronal adaptations to changes in the social dominance status of crayfish.

The effect of superfused serotonin (5-HT; 50 microns) on the synaptic responses of the lateral giant (LG) interneuron in crayfish was found to depend on the social status of the animal. In socially isolated animals. 5-HT persistently increased the response of LG to sensory nerve shock. After social isolates were paired in a small cage, they fought and determined their dominant and subordinate status. After 12 d of pairing, 5-HT reversibly inhibited the response of LG in the social subordinate and reversibly increased the response of LG in the social dominant crayfish. The effect of 5-HT changed approximately linearly from response enhancement to inhibition in the new subordinate over the 12 d of pairing. If, after 12 d pairing, the subordinate was reisolated for 8 d, the response enhancement was restored. If the subordinate, instead, was paired with another subordinate and became dominant in this new pair, the inhibitory effect of 5-HT changed to an enhancing effect over the next 12 d of pairing. If, however, two dominant crayfish were paired and one became subordinate, the enhancing effect of 5-HT persisted in the new subordinate even after 38 d pairing. These different effects of serotonin result from the action of two or more molecular receptors for serotonin. A vertebrate 5-HT, agonist had no effect on social isolates but reversibly inhibited the response of LG in both dominant and subordinate crayfish. The inhibitory effects of the agonist developed approximately linearly over the first 12 d of pairing. A vertebrate 5-HT2 agonist persistently increased the response of LG in isolate crayfish and reversibly increased the response of the cell in dominant and subordinate crayfish. Finally, although neurons that might mediate these effects of superfused 5-HT are unknown, one pair of 5-HT-immunoreactive neurons appears to contact the LG axon and initial axon segment in each abdominal ganglion in its projection caudally from the thorax.

Adaptation, Physiological↗

Alcohol and heightened aggression in individual mice.

The objective of the current research was to study the large individual differences in alcohol effects on aggressive behavior under systematically varied conditions in experimental protocols with mice. Three experiments were conducted with outbred Swiss-Webster derived mice that identified those individuals whose aggressive behavior was reliably heightened by low acute alcohol doses. In all experimental protocols, low alcohol doses were orally administered to a "resident" male mouse that subsequently confronted an "intruder" opponent for 5 min while all salient elements of aggressive behavior and motor activities were quantified. In all three experiments, alcohol (1.0 g/kg) heightened aggressive behavior by at least two standard deviations of the individual's water vehicle control mean in 27% of the mice. In 64% of mice, no reliable change in aggressive behavior was detected after the identical alcohol treatment, and in 9% of the mice alcohol decreased aggressive behavior. Experiments differed in protocol indicating that these aggression-heightening effects were evident in resident mice that were either maintained at restricted or unlimited amounts of food, housed singly or in breeding pairs with a female partner, and conditioned to perform daily a food-reinforced task or remained undisturbed. The first experiment found the aggression-heightening effects to persist during weekly challenges for at least 2 months (n = 8 of 30). The second experiment showed these effects at intervals from 5 to 60 min after alcohol administration. Blood alcohol concentrations reached peak level within 5 to 10 min after oral administration in mice that had confronted an intruder. Those mice in whom alcohol heightened aggressive behavior (n = 21) did not differ from those that showed suppressed levels (n = 9) in terms of blood alcohol concentrations (79.6 vs. 82.4 mg%), suggesting that the intensity and frequency of aggressive behavior after alcohol were not directly dependent on the amount of alcohol in the circulation. The third experiment revealed that alcohol's (0.1 to 5.6 g/kg) effects on heightened aggressive behavior (n = 11) are dissociated from those on concurrently measured high- or low-rate operant performance as engendered by a multiple FR 30-FI 600 sec schedule of reinforcement. Current results indicate that this alcohol effect is relatively specific to aggressive behavior in individual animals, offering the opportunity for neuropharmacological and molecular characterization.

Aggression↗

Interaction of beta-adrenoceptor agonists with the serotonergic system in rat brain. A behavioral study using the L-5-HTP syndrome.

The effect of beta-adrenoceptor agonists on the behavioral effect of L-5-HTP in rats and mice was studied. All beta-agonists potentiated the behavioral syndrome elicited by L-5-HTP. However no indication for a correlation between their potencies to stimulate peripheral beta-receptors and their potencies to enchance L-5-HTP effect was found. The potentiating effect of salbutamol in rats was intensified by the MAO A inhibitor clorgyline, completely inhibited by (+/-)-propranolol and partly inhibited by WB-4101, while practolol was without effect. Lesions of 5-HT pathways by i.c.v. injections of 5,7-DHT impaired the potentiating effect of salbutamol in rats. In contrast, 6-OHDA lesions or alpha-methyl-p-tyrosine pretreatment were without effect. A central site of action of salbutamol is suggested by the fact that it intensified L-5-HTP effects also after i.c.v. administration. Therefore the results suggest that salbutamol facilitates 5-HT transmission in rat brain probably via stimulation of central beta receptors.

5,7-Dihydroxytryptamine↗

Escalated aggression as a reward: corticosterone and GABA(A) receptor positive modulators in mice.

RATIONALE: Individuals seek out the opportunity to fight, but the mechanisms behind this positively reinforcing effect of aggression have yet to be understood. OBJECTIVES: The aims of this study were to (1) describe behavioral and corticosterone elevations that occur in aggressive mice conditioned to respond for the opportunity to fight another mouse, (2) determine if corticosterone elevations are necessary for operant responding and escalated aggression, and (3) determine if corticosterone elevations alter the aggression-heightening effects of gamma-aminobutyric acid (GABA)(A) receptor positive modulators. METHODS AND RESULTS: Aggressive male CFW mice were conditioned to respond under the control of a fixed-interval 10-min (FI10) schedule that reinforced their operant behavior by the presentation of an intruder mouse into their home cage. After the FI10, aggressive behavior was ca. 75% higher than the species-typical levels of fighting and plasma corticosterone was more than twice as high after briefly fighting and/or responding on the FI10 schedule. Inhibition of corticosterone synthesis by metyrapone (30-100 mg/kg) reduced both conditioned responding as well as the aggressive behavior after the FI. Although the benzodiazepine midazolam (0.3-3 mg/kg) heightened species-typical aggressive behavior, it did not increase the high level of aggression engendered by the FI schedule. However, midazolam (0.3 mg/kg) and the neurosteroid allopregnanolone (17 mg/kg) both heightened aggression when given after corticosterone synthesis inhibition by metyrapone (56 mg/kg). CONCLUSIONS: These data suggest that corticosterone elevations are required for responding that is motivated by aggressive behavior and for escalated aggression that follows this responding. Corticosterone elevations also appear to inhibit the aggression heightening effect of GABA(A) receptor positive modulators.

Aggression↗