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Dynamic interactions of behavior and amine neurochemistry in acquisition and maintenance of social rank in crayfish.

This review summarizes a set of experimental approaches with which we explore fighting behavior in crayfish and the importance of aminergic systems in its control. Our results illustrate that agonistic behavior in crustaceans can be characterized within a quantitative framework, that different types of behavioral plasticity in aggressive behavior are in need of physiological explanation, and that pharmacological intervention involving serotonergic systems produces characteristic changes in fighting. Moreover, we attempt to identify changes in neurochemistry during the acquisition of social status. Many of the studies presented here summarize ongoing work. Nonetheless, results to date complement and extend previous detailed physiological, morphological and biochemical studies exploring the roles of amines in aggression.

Aggression↗

The effect of testosterone on the behavior and coloration of adult male cichlid fish (Haplochromis burtoni, Günther).

The African cichlid fish Haplochromis burtoni shows specific behavioral responses to the intramuscular injection of testosterone. Approaching and attacking were significantly increased by injections, while six other observed behaviors remained unchanged. The results suggest that the injected testosterone affected the control of both sexual and agonistic behaviors.

Animals↗

Non-optical releasers for aggressive behavior in blind and blinded Astyanax (Teleostei, Characidae).

Prior to this study, it was believed that epigean and hypogean Astyanax differ markedly in their display of agonistic behavior. Research suggested that surface-dwelling individuals were extremely aggressive whereas their blind, cave-dwelling counterparts tended to show little or no aggressive behavior. Aggression in Astyanax was thought to be triggered by visual stimuli because surface fish in a dark environment or surface fish blinded late in life did not show aggression. Here, we demonstrate that surface fish blinded early on in their embryonic development are highly aggressive as adults. We also report the first case of a population of blind cave-dwelling Astyanax that is highly aggressive. We conclude that reduced aggression is not the only evolutionary pathway for troglobitic Astyanax and that there is some degree of developmental plasticity in the releaser of aggression and in the selection of its triggering stimuli.

Aggression↗

Behavioral sensitization to apomorphine in adult rats exposed to cocaine during the preweaning period: a preliminary study.

Sixty-day-old rats treated with cocaine (50 mg/kg SC) during postnatal days (PND) 11-20 received daily injections of apomorphine (2.0 mg/kg SC) for 10 consecutive days to examine the development of sensitization to a direct dopamine agonist. Behavior was monitored on days 1, 5, and 10, using a photobeam system, and on day 10 using the videotape assessments as well. Locomotor sensitization to apomorphine developed in the preweaning vehicle-treated males only. Neither the cocaine-treated males nor any females exhibited locomotor sensitization to repeated apomorphine injections at 2 mg/kg. There were no other treatment-related effects except for grooming, which showed an interaction between treatment and gender. Overall, every behavior analyzed showed significant apomorphine effects, except rearing. Margin time (wall hugging), grooming, and quiet were significantly decreased by apomorphine, while locomotion and the duration of sniffing were increased. In summary, these data indicate that with respect to locomotor activity, the development of sensitization to apomorphine at 2.0 mg/kg is prevented by preweaning cocaine administration in males. These data further suggest that developmental cocaine exposure produces long-term alterations in DA D1 receptor-mediated responses in male rats.

Animals↗

Effects of n-di-propylacetate on aggressive behavior and brain GABA level in isolated mice.

n-di-Propylacetate (nDPA, valproate) a GABA-T inhibitor, injected IP at the dose of 300 mg/kg antagonized agonistic behavior of isolated DBA/2 mice in a time-dependent fashion in parallel to an increase of GABA levels in olfactory bulb, striatum, posterior colliculus and septum. After 75 min, aggressive responses were higher than those after 15 to 45 min and significantly lower in comparison with those of saline injected mice. After 120 min aggressive behavior was not different from that of control mice. The concentration of GABA in the striatum and olfactory bulb returned to control value 75 and 120 min after drug administration, respectively. After 120 min GABA levels in posterior colliculus and septum were lower than those after 15 to 75 min, although significantly higher in comparison with those of saline injected mice. The results are discussed in terms of the possible involvement of olfactory bulb and striatum in GABA-mediated control of isolation-induced aggressive behavior in mice.

Aggression↗

Proline residue 280 in the second extracellular loop (EC2) of the VPAC2 receptor is essential for the receptor structure.

Inspection of the amino acid sequence of the human VPAC1 and the VPAC2 receptors after alignment of the conserved residues indicates that the second extracellular loop (EC2) is one amino acid shorter in the VPAC1 receptor due to the lack of a proline residue in position 294. We hypothesized that this could be of importance for receptor structure and/or for ligand recognition. Insertion by directed mutagenesis of a proline in that position ( 294 VPAC1) had little consequence on the binding of several agonists but reduced the affinity for the VPAC1 antagonist. Coupling of the 294 VPAC1 receptor to adenylate cyclase was improved, as demonstrated by an increased affinity for VIP and other agonists, and by a shift of the VPAC1 antagonist to partial agonist behavior. Deletion of the proline 280 (DeltaPro280 VPAC2) in the VPAC2 receptor markedly reduced the apparent affinity for all the agonists tested. Replacement of the proline by a glycine residue had a smaller effect on the ligands affinities. The proline residue in the VPAC2 receptor EC2 is thus essential for the receptor structure, and the EC2 domain is involved in ligand recognition and receptor functionality.

Adenylyl Cyclases↗

Personality traits in captive lion-tailed macaques (Macaca silenus).

Personality influences an individual's perception of a situation and orchestrates behavioral responses. It is an important factor in elucidating variation in behavior both within and between species. The major focus of this research was to test a method that differs from those used in most previous personality studies, while investigating the personality traits of 52 captive lion-tailed macaques from four zoos. In this study, data from behavioral observations, a P-type principal components analysis (PCA), and bootstrapped confidence intervals as criteria for judging the significance of factor loadings were used rather than subjective ratings, R-type factor analyses, and arbitrary rules of thumb to determine significance. We investigated the relationships among individual component scores and sex, hormonal status, and dominance rank (controlling for age and social group) using a multiple regression analysis with bootstrapped confidence intervals. Three personality dimensions emerged from this analysis: Component 1 contained Extraversion-like behaviors related to sociability and affiliativeness. The higher mean Component score for females suggests that they are more "extraverted" than males. Only agonistic behaviors were significantly related to component 2. High-ranking individuals exhibited higher mean Component 2 scores than mid- or low-ranked individuals. Bold and cautious behaviors both loaded positively on Component 3, suggesting a dimension related to curiosity. The mean Component 3 score for females was higher than the mean score for males. The method used in this study should facilitate intraspecific and general interspecific comparisons. Developing a standardized trait term list that is applicable to many species, and collecting trait term data in the same manner and concurrent with behavioral observations (and physiologic measures when feasible) could prove useful in primate research and should be explored.

Animals↗

Opiate involvement in postpartum aggression in rats.

Opiates and the endogenous opioids mediate maternal behavior and various forms of aggression. The present study sought to investigate the role of opiates in postpartum aggression (PPA), an intense form of agonistic behavior displayed by lactating females. Primiparous rats were screened for their PPA against adult males on day seven postpartum. They were then randomly assigned to one of four treatment groups [morphine, 5.0 mg/kg; naloxone alone, 0.5 mg/kg; morphine (5.0 mg/kg) plus naloxone (0.5 mg/kg); and saline] and tested for PPA on postpartum days eight and nine following the respective treatments. Morphine significantly lowered PPA, and naloxone antagonized the effect. Whereas the morphine plus naloxone, naloxone alone, and saline groups exhibited higher levels of PPA than that shown by the morphine group, there were no differences in PPA found among the morphine plus naloxone, naloxone alone, or saline groups. These results, in conjunction with evidence describing the state of the endogenous opioid system in the postpartum rat, suggest that some aspect of the endogenous opioid system may be involved in another form of maternal behavior, postpartum aggression.

Aggression↗

Subordination stress: behavioral, brain, and neuroendocrine correlates.

In mixed-sex rat groups consistent asymmetries in offensive and defensive behaviors of male dyads are associated with the development of dominance hierarchies. Subordinate males can be differentiated from dominants on the basis of both agonistic and non-agonistic behaviors, wound patterns, weight changes. Their behavior changes suggest chronic defensiveness and are also broadly isomorphic to many of the symptoms of depression; their voluntary alcohol consumption increases, and their life-spans are shortened. Both subordinate and dominant males tend to show organ change compared to non-grouped controls, with adrenal and spleen enlargement and thymus reduction. However, these changes appear to be more marked in subordinates, and only subordinates show reduced testes weights. Basal corticosterone (CORT) levels were sharply higher, and plasma testosterone (T) sharply lower, in subordinates compared to both dominants and controls, and reduced corticosterone binding globulin further enhanced free CORT for subordinates particularly. Many subordinates failed to show a normal CORT response to restraint stress. Subordinates also appear to show widespread changes in serotonin systems, with increased 5-HIAA/5-HT ratios in a number of brain areas, and alterations of 5-HT1A receptor binding at some sites. These changes suggest that subordination, a common and consistent feature of life for many animals living in social groups, may be a particularly relevant model for investigating the behavioral, neural and endocrine correlates of chronic stress.

Aggression↗

Kin recognition by paternal half-siblings in captive Papio cynocephalus.

Our objective in this study was to evaluate whether a group of paternally related, subadult baboons (Papio cynocephalus) would preferentially interact with kin or nonkin when they had been raised apart from kin other than their mothers. Subjects and their mothers were removed from the breeding group and placed in alternate housing within 24 h after birth to ensure that the subjects would not have a social history with either their sire or their half-siblings. At 90 days of age, the 23 subjects were separated from their mothers and assigned to a peer-peer social group. Behavioral performance was measured using focal animal sampling techniques and 12 molecular behavioral criteria. Analyses of the data indicate that in dyadic interactions kin did not interact more frequently than nonkin in performance of affiliative, sociosexual, and agonistic behaviors. The hypothesis that baboons recognize kin in the absence of maternal associations was not supported by the data; moreover, we suggest that social learning and social history are the most likely mechanisms for kin recognition.

Animals↗

Potential stock differences in the social behavior of rats in a situation of restricted access to food.

The social behavior of outbred Long-Evans (LE) and Wistar (WI) rats was compared in a situation where access to food was particularly difficult (clearing an aquatic barrier, plus the necessity of carrying the food back to the home cage). In groups of either six WI or LE rats, only about 50% of individuals carried the food, and the others survived by attacking those that did. However, behavioral profiles associated with these acts were different in the two cases: LE carriers, contrary to WI carriers, restole some food, and LE noncarriers expressed more agonistic behavior and were more often attacked than were the WI noncarriers. Food flow and all associated, interactive behaviors were more complex in the LE than in the WI rats, indicating the likelihood of potential genetic differences in this testing situation.

Aggression↗

Medial hypothalamic lesions in the rat enhance reactivity and mouse killing but not social aggression.

In rats subjected to lesions of the medial hypothalamus, 8 of 11 animals became mouse killers and all manifested some degree of hyperreactivity to the experimenter. When introduced as intruders into a mixed sex colony group, the lesioned rats did not manifest piloerection nor did they emit flank attacks characteristic of social aggressive behavior. However, the lesioned animals did respond to the attacks of the resident male rats with significantly more counterattacks and biting than did sham-lesioned control rats. Spontaneous mouse killing rats also failed to show a level of social aggressive behavior significantly greater than that of sham-operated control rats, but the spontaneous mouse killers did kill rat pups in the colony groups. Alpha-male rats when introduced as an intruder into a colony group did exhibit piloerection and emit flank attacks characteristic of social aggressive behavior. These results demonstrate that the mouse killing and heightened reactivity associated with medial hypothalamic lesions do not represent an indiscriminant release of all forms of agonistic behavior.

Aggression↗

Homer protein increases activation of Ca2+ sparks in permeabilized skeletal muscle.

Members of the Homer family of proteins are known to form multimeric complexes capable of cross-linking plasma membrane channels (e.g. metabotropic glutamate receptor) and intracellular Ca2+ release channels (e.g. inositol trisphosphate receptor) in neurons, which potentiates Ca2+ release. Recent work has demonstrated direct interaction of Homer proteins with type 1 and type 2 ryanodine receptor (RyR) isoforms. Moreover, Homer proteins have been shown to modulate RyR-dependent Ca2+ release in isolated channels as well as in whole cell preparations. We now show that long and short forms of Homer H1 (H1c and H1-EVH1) are potent activators of Ca2+ release via RyR in skeletal muscle fibers (e.g. Ca2+ sparks) and potent modulators of ryanodine binding to membranes enriched with RyR, with H1c being significantly more potent than H1-EVH1. Homer did not significantly alter the spatio-temporal properties of the sparks, demonstrating that Homer increases the rate of opening of RyRs, with no change in the overall RyR channel open time and amount of Ca2+ released during a spark. No changes in Ca2+ spark frequency or properties were observed using a full-length H1c with mutation in the EVH1 binding domain (H1c-G89N). One novel finding with each Homer agonist (H1c and H1-EVH1) was that in combination their actions on [3H]ryanodine binding was additive, an effect also observed for these Homer agonists in the Ca2+ spark studies. Finally, in Ca2+ spark studies, excess H1c-G89N prevented the effects of H1c in a dominant negative manner. Taken together our results suggest that the EVH1 domain is critical for the agonist behavior on Ca2+ sparks and ryanodine binding, and that the coiled-coil domain, present in long but not short form Homer, confers an increase in agonist potential apparently through the multimeric association of Homer ligand.

Animals↗

Behavioral, physiologic, and habitat influences on the dynamics of Puumala virus infection in bank voles (Clethrionomys glareolus).

Populations of bank voles (Clethrionomys glareolus) were monitored during a 4-year study in southern Belgium to assess the influence of agonistic behavior, reproductive status, mobility, and distribution of the rodents on the dynamics of Puumala virus (abbreviation: PUUV; genus: Hantavirus) infection. Concordance was high between data from serologic testing and results of viral RNA detection. Wounds resulting from biting or scratching were observed mainly in adult rodents. Hantavirus infection in adults was associated with wounds in the fall, i.e., at the end of the breeding season, but not in spring. In addition, sexually active animals were significantly more often wounded and positive for infection. Hantavirus infection was associated with higher mobility in juvenile and subadult males. Seroconversions observed 6 months apart also occurred more frequently in animals that had moved longer distances from their original capture point. During nonepidemic years, the distribution of infection was patchy, and positive foci were mainly located in dense ground vegetation.

Age Factors↗

Differential effects of micro-opioid, delta-opioid and kappa-opioid receptor agonists on dopamine receptor agonist-induced climbing behavior in mice.

Interactions between the dopaminergic system and opioids have not been adequately clarified. The present study was designed to investigate the effects of micro-opioid (morphine), delta-opioid (SNC80) and kappa-opioid (U50 488H) receptor agonists on dopamine receptor agonist-induced climbing behavior in mice. Apomorphine (dopamine-receptor agonist) increased stereotyped climbing behavior, unlike methamphetamine, morphine, U-50 488H and (+/-)7-hydroxy-N,N-di-n-propyl-2-aminotetralin hydrobromide (D2-like receptor agonist). Furthermore, SKF81297 (D1 receptor agonist) and SNC80 caused climbing behavior. In addition, while morphine (20 mg/kg), but not U50 488H or SNC80, significantly attenuated high-dose apomorphine (2.0 mg/kg)-induced climbing behavior, it significantly potentiated low-dose apomorphine (0.5 mg/kg)-induced climbing behavior. These results suggest that morphine may have dual effects on the behavioral effects induced by apomorphine. Furthermore, we interestingly showed that the combination of apomorphine or SKF81297 and SNC80 enhanced frequent nonstereotypic climbing behavior, suggesting that delta/D1 interactions may play a prominent role in the expression of certain types of behavior in mice. Thus, micro-opioid, delta-opioid and kappa-opioid receptor agonists induce possible differential effects on the dopaminergic system in mice.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Animal models of social stress: effects on behavior and brain neurochemical systems.

Social interactions serve as an evolutionarily important source of stress, and one that is virtually ubiquitous among mammalian species. Animal models of social stress are varied, ranging from a focus on acute, intermittent, or chronic exposure involving agonistic behavior, to social isolation. The relative stressfulness of these experiences may depend on the species, sex, and age of the subjects, and subject sex also appears to influence the value of hypothalamic--pituitary--adrenal (HPA) axis activity as a general criterion for stress response: higher glucocorticoid levels are typically found in dominant females in some species. Social stress models often produce victorious and defeated, or dominant and subordinate, animals that may be compared to each other or to controls, but the appropriateness of specific types of comparisons and the interpretations of their differences may vary for the different models. Social stress strongly impacts behavior, generally reducing aggression and enhancing defensiveness, both inside and outside the stress situation. Social and sexual behaviors may be reduced in subordinate animals, as is activity and responsivity to normally rewarding events. However, some components of these changes may be dependent on the presence of a dominant, rather than representing a longer-term and general alteration in behavior. Social stress effects on brain neurotransmitter systems have been most extensively investigated, and most often found in serotonin and noradrenergic systems, with changes also reported for other monoamine and for peptidergic systems. Morphological changes and alterations of neogenesis and of cell survival particularly involving the hippocampus and dentate gyrus have been reported with severe social stress, as have longer-term changes in HPA axis functioning. These findings indicate that social stress models can provide high magnitude and appropriate stressors for research, but additionally suggest a need for caution in interpretation of the findings of these models and care in analysis of their underlying mechanisms.

Animals↗

The psychopharmacological basis of nicotine's differential effects on behavior: individual subject variability in the rat.

Nicotine, the presumed active pharmacological agent in tobacco, produces variable effects on behavior that are at best described as "paradoxical" in nature. Thus, nicotine, via tobacco use in humans or nicotine administration in experimental animals, tends to transpose behavior depending on predrug baseline rates of behavior. High rates of behavior appear to be reduced, while low rates of behavior appear to be increased by nicotine. This work further proposes that nicotine's variable effects on behavior may be related to its capacity to act as a behavioral agonist and/or antagonist via its ability either to activate or to desensitize distinct central nicotinic acetylcholinergic receptors (nAChR's). Nicotine is portrayed as a neuronal modulating agent that can affect behavior contingent upon the genetic makeup of the individual subject being studied. Depending on the structure, function, and location of distinct nAChR's, nicotine appears to be able to induce a wide range of behavioral effects important to the tobacco user. However, this does not rule out the role the importance that other biogenic amine systems (i.e., serotonin or dopamine) may have in the genetics of tobacco use or nicotine's variable effects on behavior.

Acetylcholine↗

Hormone-like behavioral effects of levonorgestrel and its metabolites in the male rat.

Levonorgestrel (LNG), a contraceptive progestin, exhibits, besides its progestational activity, other hormone-like effects at the peripheral level. To assess whether LNG and its metabolites exert androgenic and/or estrogenic actions at the central nervous system (CNS), their effects on male sexual behavior in castrated rats were examined. LNG, 5alpha-dihydro LNG (5alphaLNG), and the 3alpha,5alpha- and 3beta,5alpha-tetrahydro derivatives of LNG (3alphaLNG and 3betaLNG, respectively) were administered for 3 weeks either alone (1000 microg/day) or in combination (300 microg/day) with 5alpha-dihydrotestosterone (DHT, 300 microg/day) or with estradiol-17beta (E(2), 5 microg/day). Copulatory behavior was assessed twice per week and sex accessory organs weights recorded at the end of treatments. LNG restored full copulatory behavior comparable to that of testosterone treated animals, although with a slight delay, whereas 5alphaLNG induced male sexual behavior in a significantly lower number of subjects. 3betaLNG and 3alphaLNG induced mounting but failed to restore intromission and ejaculation. Combined LNG+E(2) treatment fully activated mounting and intromission, but ejaculation was only partially restored. Combined 5alphaLNG+E(2) treatment and the combinations of 3alphaLNG or 3betaLNG with E(2) were significantly less effective, activating fewer intromissions and ejaculations. 3alphaLNG and 5alphaLNG, in combination with DHT, restored male sexual behavior. LNG, but not its metabolites, induced a significant increase on the weight of sex accessory organs. The overall results demonstrated that high doses of LNG induce a potent androgen agonistic behavioral effect and that its A-ring reduction diminishes this potency and enables a shift towards a weak estrogen-like effect.

Androgens↗