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Biomedical subjects

Cliff H Summers

Publications and source records attributed to Cliff H Summers.

At least 19 recordsLinked to original sources

Rapid neuroendocrine responses evoked at the onset of social challenge.

At the onset of agonistic social challenge, individuals must assess the degree of threat the opponent represents in order to react appropriately. We aimed to characterize the neuroendocrine changes accompanying this period of initial social assessment using the lizard Anolis carolinensis. Conveyance of aggressive intent by male A. carolinensis is facilitated by rapid postorbital skin darkening (eyespot), whereas eyespot presence inhibits opponent aggression. By manipulating this visual signal, we also investigated whether differing neuroendocrine changes were evoked by initial presentation of varying levels of social threat. Subjects were painted postorbitally either with black paint (high threat level), green paint (low threat level) or water (controls). Painted animals were presented with a mirror and sampled immediately upon exhibiting aggressive intent towards the reflected simulated opponent, but before producing behaviors such as motor pattern-based displays. Control animals (blank surface presented) were sampled at times derived from averaging response times of painted subjects. Brains and plasma were analyzed for monoamine activity and catecholamine levels using electrochemical HPLC. Social threat evoked increases in plasma catecholamine levels indistinguishable from those caused by brief environmental disturbance. However, brief social challenge caused distinct rapid increases in amygdala and nucleus accumbens (NAc) dopamine and serotonin levels. Amygdalar changes were associated with general social threat presence, but NAc monoamines were affected by both threat level and subject motivation to engage in confrontation. This suggests that specific rapid activity changes in key forebrain limbic nuclei differ according to the degree of social threat perceived at the start of the interaction.

Aggression↗

Evolutionary background for stress-coping styles: relationships between physiological, behavioral, and cognitive traits in non-mammalian vertebrates.

Reactions to stress vary between individuals, and physiological and behavioral responses tend to be associated in distinct suites of correlated traits, often termed stress-coping styles. In mammals, individuals exhibiting divergent stress-coping styles also appear to exhibit intrinsic differences in cognitive processing. A connection between physiology, behavior, and cognition was also recently demonstrated in strains of rainbow trout (Oncorhynchus mykiss) selected for consistently high or low cortisol responses to stress. The low-responsive (LR) strain display longer retention of a conditioned response, and tend to show proactive behaviors such as enhanced aggression, social dominance, and rapid resumption of feed intake after stress. Differences in brain monoamine neurochemistry have also been reported in these lines. In comparative studies, experiments with the lizard Anolis carolinensis reveal connections between monoaminergic activity in limbic structures, proactive behavior in novel environments, and the establishment of social status via agonistic behavior. Together these observations suggest that within-species diversity of physiological, behavioral and cognitive correlates of stress responsiveness is maintained by natural selection throughout the vertebrate sub-phylum.

Adaptation, Psychological↗

Uterine motility in the reptile Anolis carolinensis: interactive effects of tension, prostaglandins, calcium, and vasotocin.

Uteri of Anolis carolinensis exhibited spontaneous rhythmic contractions in vitro. Addition of arginine vasotocin (AVT) caused an immediate, strong, tonic contraction followed by rhythmic contractions with the same frequency as spontaneous contractions but of a greater amplitude. At low tension (1.5 g) the AVT-induced tonic contraction was blocked by low dose of indomethacin, suggesting that it is influenced by calcium rather than prostaglandins (PGs). An increase in tension (from 1.5 to 15 g) reduced the duration of the AVT-induced tonic contraction; this stretch-induced decrease was also blocked by indomethacin. Stretch also decreased the duration of the rhythmic contractions, but this stretch effect was not inhibited by indomethacin. The rest interval between rhythmic contractions was decreased by PGF2alpha and PGE2, and indomethacin or stretch blocked these PG effects. Indomethacin, AVT, or stretch alone did not affect PGF2alpha secretion from AVT-treated uteri. Stretch also reduced PGF2alpha secretion from AVT-treated uteri, an effect inhibited by indomethacin.

Animals↗

Dopaminergic activity modulation via aggression, status, and a visual social signal.

Social interaction may elicit aggression, establish social rank, and be influenced by changes in central dopaminergic activity. In the lizard Anolis carolinensis, a sign stimulus (darkening of postorbital skin or eyespots) inhibits aggressive response from opponents, in part because it forms more rapidly in dominant males. The authors report that artificially hiding or darkening eyespots influences central dopaminergic activity, social status, and aggression during dyadic social interaction. All males that viewed an opponent with eyespots painted black became subordinate and exhibited elevated dopamine in raphe, lateral amygdala, and medial amygdala but decreased dopamine in septum and locus ceruleus. In contrast, males that viewed opponents with hidden eyespots (painted green) became dominant and had increased dopamine in striatum, nucleus accumbens, hypothalamus, and combined substantia nigra/ventral tegmental area.

Aggression↗

Interactions between the neural regulation of stress and aggression.

Socially aggressive interaction is stressful. What is more, social aggression is stressful for both dominant and subordinate animals. Much of the neurocircuitry for stress and aggression overlap. The pattern of neurochemical and hormonal events stimulated by social interaction make it clear that subtle differences in this pattern of response distinguish social rank. The neurotransmitter serotonin (5-HT) responds rapidly to stress, and also appears to play the most important role for inhibitory regulation of aggressive interactions. In addition, the adrenocortical/interrenal steroid hormones corticosterone and cortisol are responsive to stress and influence aggression. However, while 5-HT and glucocorticoids can both be inhibitory to aggression, the relationship between 5-HT and glucocorticoids is not straightforward, and much of the distinctions in function depend upon timing. Neither is inhibitory during the early stressful phase of aggression. This transmitter-hormone combination follows and influences a four-stage functional pattern of effect: (1) predisposed (positively or negatively) toward aggression, (2) motivated toward behavior, (3) responsive to stress (including aggression) and passively allowing aggression, and finally (4) chronically applied 5-HT and glucocorticoids inhibit aggression.

Aggression↗

Glucocorticoid interaction with aggression in non-mammalian vertebrates: reciprocal action.

Socially aggressive interaction is stressful, and as such, glucocorticoids are typically secreted during aggressive interaction in a variety of vertebrates, which may both potentiate and inhibit aggression. The behavioral relationship between corticosterone and/or cortisol in non-mammalian (as well as mammalian) vertebrates is dependent on timing, magnitude, context, and coordination of physiological and behavioral responses. Chronically elevated plasma glucocorticoids reliably inhibit aggressive behavior, consistent with an evolutionarily adaptive behavioral strategy among subordinate and submissive individuals. Acute elevation of plasma glucocorticoids may either promote an actively aggressive response via action in specialized local regions of the brain such as the anterior hypothalamus, or is permissive to escalated aggression and/or activity. Although the permissive effect of glucocorticoids on aggression does not suggest an active role for the hormone, the corticosteroids may be necessary for full expression of aggressive behavior, as in the lizard Anolis carolinensis. These effects suggest that short-term stress may generally be best counteracted by an actively aggressive response, at least for socially dominant proactive individuals. An acute and active response may be evolutionarily maladaptive under chronic, uncontrollable and unpredictable circumstances. It appears that subordinate reactive individuals often produce compulsorily chronic responses that inhibit aggression and promote submissive behavior.

Aggression↗

Serotonin metabolism in directly developing frog embryos during paternal care.

Central serotonin (5-HT) metabolism during embryogenesis and a 3-day post-hatching period was analyzed using high performance liquid chromatography in the directly developing frog, Eleutherodactylus coqui. This anuran bypasses the free-swimming larval stage and embryos hatch as miniature frogs in the adult phenotype. During embryogenesis and for a short time immediately after hatching, male E. coqui provide paternal care by brooding and guarding eggs/embryos to prevent desiccation and predation. Serotonin and its catabolite, 5-HIAA, were measured from whole brain during embryogenesis and at 3 days post-hatch to identify critical periods in 5-HT development and to determine the relationship between 5-HT and life history events such as hatching and frog dispersal from the nest site. Serotonergic activity was highest during the early-mid embryonic stages as indicated by the ratio of 5-HIAA/5-HT, a general indicator of turnover and metabolism. There were significant increases in tissue concentrations of 5-HT during the latest or terminal embryonic stage, just prior to hatching, and also at 3 days post-hatch, shortly before neonates disperse into the rainforest. These two increases probably represent different functional requirements during development. The first may occur as a result of the surge of development in the 5-HT system during late embryogenesis that occurs in E. coqui and the second may be from the increase demand in sensory and motor neural development required before dispersal from the nest site.

Animals↗

Ontogeny of central serotonergic neurons in the directly developing frog, Eleutherodactylus coqui.

Embryonic development of the central serotonergic neurons in the directly developing frog, Eleutherodactylus coqui, was determined by using immunocytochemistry. The majority of anuran amphibians (frogs) possess a larval stage (tadpole) that undergoes metamorphosis, a dramatic post-embryonic event, whereby the tadpole transforms into the adult phenotype. Directly developing frogs have evolved a derived life-history mode where the tadpole stage has been deleted and embryos develop directly into the adult bauplan. Embryonic development in E. coqui is classified into 15 stages (TS 1-15; 1 = oviposition/15 = hatching). Serotonergic immunoreactivity was initially detected at TS 6 in the raphe nuclei in the developing rhombencephalon. At TS 7, immunopositive perikarya were observed in the paraventricular organ in the hypothalamus and reticular nuclei in the hindbrain. Development of the serotonergic system was steady and gradual during mid-embryogenesis. However, starting at TS 13 there was a substantial increase in the number of serotonergic neurons in the paraventricular, raphe, and reticular nuclei, a large increase in the number of varicose fibers, and a differentiation of the reticular nuclei in the hindbrain. Consequentially, E. coqui displayed a well-developed central serotonergic system prior to hatching (TS 15). In comparison, the serotonergic system in metamorphic frogs typically starts to develop earlier but the surge of development that transpires in this system occurs post-embryonically, during metamorphosis, and not in the latter stages of embryogenesis, as it does in E. coqui. Overall, the serotonergic development in E. coqui is similar to the other vertebrates.

Animals↗

Stress induces rapid changes in central catecholaminergic activity in Anolis carolinensis: restraint and forced physical activity.

Immobilization stress and physical activity separately influence monoaminergic function. In addition, it appears that stress and locomotion reciprocally modulate neuroendocrine responses, with forced exercise ameliorating stress-induced serotonergic activity in lizards. To investigate the interaction of forced physical activity and restraint stress on central dopamine (DA), norepinephrine (NE), and epinephrine (Epi), we measured these catecholamines and their metabolites in select brain regions of stressed and exercised male Anolis carolinensis lizards. Animals were handled briefly to elicit restraint stress, with some lizards additionally forced to run on a track until exhaustion, or half that time (50% of average time to exhaustion), compared to a control group that experienced no restraint or exercise. Norepinephrine concentrations in the hippocampus and locus ceruleus decreased with restraint stress, but returned to control levels following forced exhaustion. Levels of NE in the raphé nuclei and area postrema, and epinephrine in raphé became elevated following restraint stress, and returned to control levels following forced physical activity to 50% or 100% exhaustion. Striatal DA increased as animals were exercised to 50% of exhaustion, and returned to baseline with exhaustion. At exhaustion, striatal Epi levels were diminished, compared with controls. In the area postrema, exhaustion reversed a decline in epinephrine levels that followed forced physical activity. These results suggest that stress stimulates a rapid influence on central catecholamines. In addition, forced exercise, and even exhaustion, may alleviate the effects of restraint stress on central monoamines.

Animals↗

Does serotonin influence aggression? comparing regional activity before and during social interaction.

Serotonin is widely believed to exert inhibitory control over aggressive behavior and intent. In addition, a number of studies of fish, reptiles, and mammals, including the lizard Anolis carolinensis, have demonstrated that serotonergic activity is stimulated by aggressive social interaction in both dominant and subordinate males. As serotonergic activity does not appear to inhibit agonistic behavior during combative social interaction, we investigated the possibility that the negative correlation between serotonergic activity and aggression exists before aggressive behavior begins. To do this, putatively dominant and more aggressive males were determined by their speed overcoming stress (latency to feeding after capture) and their celerity to court females. Serotonergic activities before aggression are differentiated by social rank in a region-specific manner. Among aggressive males baseline serotonergic activity is lower in the septum, nucleus accumbens, striatum, medial amygdala, anterior hypothalamus, raphe, and locus ceruleus but not in the hippocampus, lateral amygdala, preoptic area, substantia nigra, or ventral tegmental area. However, in regions such as the nucleus accumbens, where low serotonergic activity may help promote aggression, agonistic behavior also stimulates the greatest rise in serotonergic activity among the most aggressive males, most likely as a result of the stress associated with social interaction.

Aggression↗

Effects of L-DOPA on aggressive behavior and central monoaminergic activity in the lizard Anolis carolinensis, using a new method for drug delivery.

The dopamine (DA) precursor, L-DOPA (500 microg), was injected into living crickets, which were ingested (one each) by adult male Anolis carolinensis. This method of delivery elevated plasma L-DOPA and DA concentrations by approximately 1000-fold. In contrast, plasma epinephrine (Epi) and norepinephrine (NE) were not influenced by L-DOPA treatment, although they were elevated following the consumption of the cricket. Lizards that ingested L-DOPA treated crickets had elevated L-DOPA in all brain regions measured, with DA and/or DOPAC also increased significantly in most brain regions studied. Despite increased DA levels in the striatum and nucleus accumbens as a response to L-DOPA, the treatment had no influence on general motor activity. Central serotonin, NE, and Epi systems were not affected in any brain region by oral L-DOPA treatment. In addition, aggression was inhibited by this dose of L-DOPA, even though there was no effect on serotonergic systems. This is surprising because controlling aggressive behavior is usually considered the province of serotonergic activity. Aggression was measured before and after treatment, and while saline-treated lizards retained the full vigor of aggressive activity, those fed a cricket injected with L-DOPA were only one-third as aggressive after treatment. As L-DOPA treatment did not affect general motor activity, the effect appears to be directly associated with aggression. This is supported by the observation that L-DOPA treatment delayed latency to eyespot darkening, which predicts the latency to aggression.

Administration, Oral↗

Dynamics and mechanics of social rank reversal.

Stable social relationships are rearranged over time as resources such as favored territorial positions change. We test the hypotheses that social rank relationships are relatively stable, and although social signals influence aggression and rank, they are not as important as memory of an opponent. In addition, we hypothesize that eyespots, aggression and corticosterone influence serotonin and N-methyl-D: -aspartate (NMDA) systems in limbic structures involved in learning and memory. In stable adult dominant-subordinate relationships in the lizard Anolis carolinensis, social rank can be reversed by pharmacological elevation of limbic serotonergic activity. Any pair of specific experiences: behaving aggressively, viewing aggression or perceiving sign stimuli indicative of dominant rank also elevate serotonergic activity. Differences in the extent of serotonergic activation may be a discriminating and consolidating factor in attaining superior rank. For instance, socially aggressive encounters lead to increases in plasma corticosterone that stimulate both serotonergic activity and expression of the NMDA receptor subunit 2B (NR(2B)) within the CA(3) region of the lizard hippocampus. Integration of these systems will regulate opponent recognition and memory, motivation to attack or retreat, and behavioral and physiological reactions to stressful social interactions. Contextually appropriate social responses provide a modifiable basis for coping with the flexibility of social relationships.

Aggression↗

Social stress affects circulating melatonin levels in rainbow trout.

In salmonid fishes there are indications that socially subordinate individuals avoid competition with larger, dominant fish by adjusting daily feeding and activity cycles. As in other vertebrates, the pineal organ and its hormone melatonin act as synchronizers of daily rhythms to the external light/dark cycle in salmonids. Social defeat may act as a potent stressor; inducing elevated glucocorticoid secretion and a general behavioral inhibition. Here, we show that social stress also affects circulating melatonin levels in rainbow trout, a species known to display strong dominance hierarchies both in the wild and under captive rearing. Subordinate individuals had significantly higher nighttime melatonin levels than dominant fish or controls. There was no effect of social rank on the much lower melatonin levels observed in animals sampled during the day. Correlations between circulating glucocorticoids and melatonin depended on circadian cycles as well as social context. This study suggests that altered melatonin production contributes to the physiological and behavioral profile of subordinate animals. Social status, and other determinants of the stress level of experimental animals, therefore should be taken into consideration as potential factors influencing the results from in vivo research on this hormone.

Agonistic Behavior↗

Development of the nasal chemosensory organs in two terrestrial anurans: the directly developing frog, Eleutherodactylus coqui (Anura: Leptodactylidae), and the metamorphosing toad, Bufo americanus (Anura: Bufonidae).

Nearly all vertebrates possess an olfactory organ but the vomeronasal organ is a synapomorphy for tetrapods. Nevertheless, it has been lost in several groups of tetrapods, including aquatic and marine animals. The present study examines the development of the olfactory and vomeronasal organs in two terrestrial anurans that exhibit different developmental modes. This study compares the development of the olfactory and vomeronasal organs in metamorphic anurans that exhibit an aquatic larva (Bufo americanus) and directly developing anurans that have eliminated the tadpole (Eleutherodactylus coqui). The olfactory epithelium in larval B. americanus is divided into dorsal and ventral branches in the rostral and mid-nasal regions. The larval olfactory pattern in E. coqui has been eliminated. Ontogeny of the olfactory system in E. coqui embryos starts to vary substantially from the larval pattern around the time of operculum development, the temporal period when the larval stage is hypothesized to have been eliminated. The nasal anatomy of the two frogs does not appear morphologically similar until the late stages of embryogenesis in E. coqui and the terminal portion of metamorphosis in B. americanus. Both species and their respective developing offspring, aquatic tadpoles and terrestrial egg/embryos, possess a vomeronasal organ. The vomeronasal organ develops at mid-embryogenesis in E. coqui and during the middle of the larval period in B. americanus, which is relatively late for neobatrachians. Development of the vomeronasal organ in both frogs is linked to the developmental pattern of the olfactory system. This study supports the hypothesis that the most recent common ancestor of tetrapods possessed a vomeronasal organ and was aquatic, and that the vomeronasal organ was retained in the Amphibia, but lost in some other groups of tetrapods, including aquatic and marine animals.

Animals↗

Stress coping style predicts aggression and social dominance in rainbow trout.

Social stress is frequently used as a model for studying the neuroendocrine mechanisms underlying stress-induced behavioral inhibition, depression, and fear conditioning. It has previously been shown that social subordination may result in increased glucocorticoid release and changes in brain signaling systems. However, it is still an open question which neuroendocrine and behavioral differences are causes, and which are consequences of social status. Using juvenile rainbow trout of similar size and with no apparent differences in social history, we demonstrate that the ability to win fights for social dominance can be predicted from the duration of a behavioral response to stress, in this case appetite inhibition after transfer to a new environment. Moreover, stress responsiveness in terms of confinement-induced changes in plasma cortisol was negatively correlated to aggressive behavior. Fish that exhibited lower cortisol responses to a standardized confinement test were markedly more aggressive when being placed in a dominant social position later in the study. These findings support the view that distinct behavioral-physiological stress coping styles are present in teleost fish, and these coping characteristics influence both social rank and levels of aggression.

Adaptation, Psychological↗

Behavioral and neuroendocrine correlates of displaced aggression in trout.

In humans and other primates, violent actions performed by victims of aggression are often directed toward an individual or object that is not the source of provocation. This psychological phenomenon is often called displaced aggression. We demonstrate that displaced aggression is either rooted in evolutionarily conserved behavioral and neuroendocrine mechanisms, or represent a convergent pattern that has arisen independently in fish and mammals. Rainbow trout that briefly encountered large, aggressive fish reacted with increased aggression toward smaller individuals. There was a strong negative correlation between received aggression and behavioral change: Individuals subjected to intense aggression were subdued, while moderate assaults induced strong agitation. Patterns of forebrain serotonin turnover and plasma cortisol suggest that the presence of socially subordinate fish had an inhibitory effect on neuroendocrine stress responses. Thus, subordinate individuals may serve as stress-reducing means of aggressive outlet, and displaced aggression toward such individuals appears to be a behavioral stress coping strategy in fishes.

Aggression↗

Monoamines stimulate sex reversal in the saddleback wrasse.

Monoamine neurotransmitters (norepinephrine, dopamine, and serotonin) play an important role in reproduction and sexual behavior throughout the vertebrates. They are the first endogenous chemical signals in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. In teleosts with behavioral sex determination, much is known about behavioral cues that induce sex reversal. The cues are social, processed via the visual system and depend on the ratio of females to males in the population. The mechanisms by which these external behavioral cues are converted to an internal chemical regulatory process are largely unknown. The protogynous Hawaiian saddleback wrasse, Thalassoma duperrey, was used to investigate the biological pathway mediating the conversion of a social cue into neuroendocrine events regulating sex reversal. Because monoamines play an important role in the regulation of the HPG axis, they were selected as likely candidates for such a conversion. To determine if monoamines could affect sex reversal, drugs affecting monoamines were used in an attempt to either induce sex reversal under non-permissive conditions, or prevent sex reversal under permissive conditions. Increasing norepinephrine or blocking dopamine or serotonin lead to sex reversal in experimental animals under non-permissive conditions. Increasing serotonin blocked sex reversal under permissive conditions, while blocking dopamine or norepinephrine retarded the process. The results presented here demonstrate that monoamines contribute significantly to the control sex reversal. Norepinephrine stimulates initiation and completion of gonadal sex of reversal as well as color change perhaps directly via its effects on the HPG axis. Dopamine exercises inhibitory action on the initiation of sex reversal while 5-HT inhibits both initiation and completion of sex reversal. The serotonergic system appears to be an integral part of the pathway mediating the conversion of a social cue into a neuroendocrine event. The complex organization of neurochemical events controlling the psychosocial, physiological, and anatomical events that constitute reversal of sexual identity includes monoamine neurotransmitters.

Adaptation, Physiological↗

Rapid glucocorticoid stimulation and GABAergic inhibition of hippocampal serotonergic response: in vivo dialysis in the lizard anolis carolinensis.

Central serotonin (5-HT) is activated during stressful situations and aggressive interactions in a number of species. Glucocorticoids secreted peripherally during stressful events feed back on central systems and may affect 5-HT mediation of stress-induced behavioral events. To test the neuromodulatory effect of stress hormone secretion, serotonin overflow was measured from the hippocampus of the lizard Anolis carolinensis. Microdialysis was used to collect repeated samples from anesthetized lizards, with perfusate measured by HPLC with electrochemical analysis. Following initially high levels of 5-HT, concentrations stabilized to basal levels after approximately 2 h. Intracortical infusion of 200 ng/ml corticosterone evoked transient increases in 5-HT release of approximately 400%. The effect of corticosterone on 5-HT overflow appears to be dose dependent as 20 ng/ml stimulated an increase of 200%, whereas 2 ng/ml stimulated a 50% increase. Administration of 0.1 and 1 ng/ml GABA via the dialysis probe significantly inhibited 5-HT overflow by 20 and 40%, respectively. The duration of GABA inhibition is greater than the stimulatory response for glucocorticoids. Short-lived glucocorticoid stimulation of 5-HT release suggests a possible mechanism for endocrine mediation of continuously changing social behavioral events.

Anesthetics, Local↗