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PubMed1993

Evaluation of the interaction of mu and kappa opioid agonists on locomotor behavior in the horse.

This study was designed to determine the interactive effects of mu and kappa opioid agonists on locomotor behavior in the horse. Three doses of a mu agonist, fentanyl (5, 10, 20 micrograms/kg) and a kappa agonist U50,488H (30, 60, 120 micrograms/kg) were administered in a random order to six horses. Locomotor activity was measured using a two minute footstep count. Each dose of U50,488H was then combined with 20 micrograms/kg of fentanyl to determine the interactive effects of the drugs on locomotor activity. A significant increase in locomotor activity was seen with 20 micrograms/kg of fentanyl and all the drug combinations. The combination of U50,488H with fentanyl resulted in an earlier onset of locomotor activity. At the highest doses of the combination (U50,488H 120 micrograms/kg, fentanyl 20 micrograms/kg), the duration of locomotor activity was significantly increased when compared to the other doses. We conclude that locomotor activity is maintained or enhanced in horses when a receptor specific kappa agonist is combined with a mu receptor agonist.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Antagonistic properties of human prolactin analogs that show paradoxical agonistic activity in the Nb2 bioassay.

Based on the assumption that the prolactin receptor (PRLR) is activated by PRL-induced sequential dimerization, potential human PRL (hPRL) antagonists were designed that sterically interfere with binding site 2. We previously reported the unexpected agonistic properties of these hPRL analogs in the rat Nb2 bioassay (Goffin, V., Struman, I., Mainfroid, V., Kinet, S., and Martial, J. A. (1994) J. Biol. Chem. 269, 32598-32606). In order to investigate whether such paradoxical agonistic behavior might result from characteristic features of the Nb2 assay (e.g. species specificity), we transfected in the same cell system the cDNA encoding the PRLR from rat or human species along with reporter genes containing PRL-responsive DNA sequences. We characterized the agonistic, self-antagonistic and/or antagonistic effects of wild type rat PRL, wild type hPRL, and three hPRL analogs, mutated either at binding site 1 or at binding site 2. Our results clearly show that the agonistic/antagonistic properties of PRLs are species-specific. We thus propose different models of receptor activation, depending on the relative affinities of each hormonal binding site, which is directed by species specificity. Finally, this is the first report of hPRL binding site 2 analogs showing antagonistic properties on human and, to a lesser extent, rat receptors.

Animals↗
PubMedDate not supplied

[The effect of the S1A-receptor agonist ipsapirone on behavior types in wild and domesticated rats].

Selective agonist of 1A subtype of serotonine receptors ipsapirone inhibited manifestation of affective kinds of aggression in wild and domesticated rats. Administration of ipsapirone (10 mg/kg) decreased the number of aggressive attacks of wild and domesticated rats in the test of shock-induced aggression and blocked manifestation of defensive reaction to the experimenter in wild rats. Neophobia in wild rats decreased under the influence of ipsapirone. At the same time ipsapirone did not change mouse-killing behaviour either in wild or in domesticated rats. Probably, 5-HT1A receptors the aggressive regulate reaction, which are parts of the complex of defensive behaviour of the wild animals.

Aggression↗
PubMedDate not supplied

Alcohol, habituation and the patterning of aggressive responses in a cichlid fish.

Territorial cichlids were presented for 30 min with a conspecific male intruder (contained in a clear glass tube). Eight hr prior, 2 groups were administered alcohol (0.15 or 0.30 percent in the aquaria water). A third group served as a control. Three responses were recorded to allow analysis of topographic changes in behavior as well as changes in absolute levels. During the habituation phase, the normal group showed a sequence of long displays, followed by shorter ones as the frequency of attacks increased. The occurrence of threat which gradually gives way to attack is characteristic of the agonistic behavior of this species. In contrast to the controls, the 0.15 percent group was hyperaggressive, while the 0.30 percent group was hypoaggressive. Furthermore, the patterning of responses were abnormal. The 0.15 percent group gave abbreviated threats and more attacks (interpreted as a tendency to attack without warning); whereas, the 0.30 percent group gave many long threat displays, but few attacks. A stimulus specificity test provided strong evidence that the waning found during the initial phase was habituation.

Aggression↗
PubMed1984

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

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

Aggression↗
PubMed2005

A series of ligands displaying a remarkable agonistic-antagonistic profile at the adenosine A1 receptor.

Adenosine receptor agonists are usually variations of the natural ligand, adenosine. The ribose moiety in the ligand has previously been shown to be of great importance for the agonistic effects of the compound. In this paper, we present a series of nonadenosine ligands selective for the adenosine A(1) receptor with an extraordinary pharmacological profile. 2-Amino-4-benzo[1,3]dioxol-5-yl-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile (70, LUF 5853) shows full agonistic behavior comparable with the reference compound CPA, while also displaying comparable receptor binding affinity (K(i) = 11 nM). In contrast, compound 58 (2-amino-4-(3-trifluoromethylphenyl)-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile, LUF 5948) has a binding affinity of 14 nM and acts as an inverse agonist. Also present within this same series are compounds that show neutral antagonism of the adenosine A(1) receptor, for example compound 65 (2-amino-4-(4-difluoromethoxyphenyl)-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile, LUF 5826).

Adenosine A1 Receptor Agonists↗
PubMed2003

Peering through the looking glass at a sexual parasite: are Amazon mollies red queens?

The gynogenetic Amazon molly (Poecilia formosa) is a clonal, all-female lineage of livebearing fish that faces an unusual obstacle to evolutionary persistence. Sperm from heterospecific males (either sailfin, P. latipinna, or Atlantic, P. mexicana, mollies) is necessary to trigger embryogenesis. However, none of the male's genes are incorporated into the genome of the gynogenetic offspring. Some investigators have proposed that the evolution of male mate discrimination is a result of this cost, leading to a coevolutionary arms race between male avoidance of P. formosa and P. formosa attractiveness. Given that P. formosa successfully reproduces and has not yet gone extinct, it is clear there are mechanisms by which they attract the sexual attention of males. Although a Red Queen coevolutionary process in typical host/parasite systems has been shown to favor the persistence of sexual species, in this system an arms race has been invoked to explain the reverse. Here I present behavioral data supporting a more parsimonious scenario: that mechanisms of attraction in P. formosa are simply a consequence of its hybrid origin. Poecilia latipinna and P. mexicana males do not discriminate between gynogenetic P. formosa females and first generation sexual hybrid females, and females do not differ in agonistic behaviors associated with competition for mates. Both results contradict predictions from the Red Queen hypothesis. Therefore, coevolution is not necessary to explain the apparent evolutionary persistence of P. formosa.

Animals↗
PubMed1992

Mirrors as enrichment for captive chimpanzees (Pan troglodytes).

At many facilities, limitations of the physical environment have reduced the opportunity for captive chimpanzees to live in large, naturalistic social groups. Convex mirrors used to increase visual access of neighboring groups may improve the social environment. This was tested in a study of 28 chimpanzees (Pan troglodytes) group-housed in conventional indoor/outdoor runs. A total of 47.8 hours of behavioral observations were conducted and comparisons made across three conditions: no mirror present, a mirror present with visual access to neighboring conspecifics, or a mirror present with visual access to the neighbors' empty run. When the mirror gave subjects visual access to neighboring animals, facial expressions, sexual, and agonistic behaviors increased, whereas affiliative behavior decreased compared with when no mirror was present. When the mirror gave subjects visual access to a neighbors' empty run, facial expressions and sexual behavior increased compared with when no mirror was present. When the mirror gave subjects visual access to a neighbor's empty run, agonism decreased compared with when a mirror gave subjects visual access to neighboring animals. When subjects had visual access to neighbors, they used the mirror 30% of the total data points; while they had visual access to the neighbors' empty run, they looked during 24% of the total data points. Juveniles' use of the mirror increased over time while adults' use remained stable. Adult males used the mirror less than did the other subjects. These findings indicate that a mirror allowing visual access to neighboring conspecifics has potential as an enrichment device that affects social behavior.

Age Factors↗
PubMed1998

Acute effects of glucocorticoids: behavioral and pharmacological perspectives.

There has been evidence since the early eighties that glucocorticoids, apart from their well known chronic effects, may have acute, short-term effects. However, a lack of understanding of the molecular mechanisms of action has hampered appreciation of these observations. Mounting evidence over the years has continued to confirm the early observations on a fast corticosterone control of acute behavioral responses. We summarize experimental data obtained mainly in rats but also in other species which show: (1) that glucocorticoid production is sufficiently quick to affect ongoing behavior; (2) that there exist molecular mechanisms that could conceivably explain the fast neuronal effects of glucocorticoids (although these are still insufficiently understood); (3) that glucocorticoids are able to stimulate a wide variety of behaviors within minutes; and (4) that acute glucocorticoid production (at least in the case of aggressive behavior) is linked to the achievement of the behavioral goal (winning). The achievement of the behavioral goal reduces glucocorticoid production. It is argued that glucocorticoids are regulatory factors having a well-defined behavioral role. Both the acute (stimulatory) effects and the chronic (inhibitory) effects are adaptive in nature. The acute control of behavior by corticosterone is a rather unknown process that deserves further investigation. The pharmacologic importance of the acute glucocorticoid response is that it may readily affect the action of pharmacologic agents. An interaction between acute glucocorticoid increases and noradrenergic treatments has been shown in the case of offensive and defensive agonistic behavior. Non-behavioral data demonstrate that acute increases in glucocorticoids may interfere with other neurotransmitter systems (e.g., with the 5HT system) as well. These observations show the importance of taking into account endocrine background and endocrine responsiveness in behavior pharmacological experiments.

Animals↗
PubMed1990

Nigral D1 and striatal D2 receptors mediate the behavioral effects of dopamine agonists.

The mediation of behavior by nigral and striatal dopamine (DA) D1 and D2 receptors was investigated in rats that had sustained extensive unilateral 6-hydroxydopamine-induced injury to ascending DA neurons. Selective D1 and D2 agonists and antagonists were injected directly into the DA-denervated substantia nigra pars reticula or the caudate-putamen via a chronically indwelling cannula. Contralateral rotation resulting from unilateral stimulation of supersensitive DA receptors was quantified over 46 min. Intrastriatal apomorphine (5 micrograms) or the selective D2 agonist quinpirole (5 micrograms), but not the selective D1 agonist (+/-)-SKF 38393 (15 micrograms), induced vigorous rotation. The rotation induced by intrastriatal quinpirole was greatly diminished by systemic administration of the selective D2 antagonist eticlopride (0.5 mg/kg, i.p.) and could not be enhanced by additional injection of intrastriatal (+/-)-SKF 38393. Intranigral administration of apomorphine or (+/-)-SKF 38393, but not quinpirole (same doses as above), elicited vigorous rotation. However, the rotation induced by intranigral (+/-)-SKF 38393 could not be blocked by systemic administration of the selective D1 antagonist SCH 23390 (0.5 mg/kg, s.c.), and was mimicked by intranigral (-)-SKF 38393 (15 micrograms), which exhibits 100-fold less activity than the dextrorotatory enantiomer at the D1 receptor. In order to circumvent the problem of this drug's apparent non-D1-mediated action when injected intranigrally, rotation was induced by systemic (+/-)-SKF 38393 (2.0 mg/kg, i.p.) 10 min after intranigral administration of selective antagonists. Intranigral SCH 23390 (10 micrograms), but not eticlopride (10 micrograms), powerfully antagonized the rotation induced by systemic (+/-)-SKF 38393. Conversely, rotation induced by systemic quinpirole (0.5 mg/kg, i.p.) was potently blocked by intrastriatal eticlopride but not SCH 23390. Rotation induced by systemic apomorphine (0.25 mg/kg, i.p.) was not attenuated by either antagonist alone, regardless of intracerebral injection site. The results indicate that both nigral D1 and striatal D2 receptors mediate the behavioral effects of DA agonists. These data may be useful in elucidating the mechanism(s) underlying the D1/D2 synergism observed in neurologically intact animals, as well as in understanding the action of drugs used in the treatment of Parkinson's disease.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

The TIPP opioid peptide family: development of delta antagonists, delta agonists, and mixed mu agonist/delta antagonists.

The discovery of the prototype delta opioid antagonists TIPP (H-Tyr-Tic-Phe-Phe-OH) and TIP (H-Tyr-Tic-Phe-OH) in 1992 was followed by extensive structure-activity relationship studies, leading to the development of analogues that are of interest as pharmacological tools or as potential therapeutic agents. Stable TIPP-derived delta opioid antagonists with subnanomolar delta receptor binding affinity and extraordinary delta receptor selectivity include TIPP[Psi] (H-Tyr-TicPsi[CH(2)NH]Phe-Phe-OH] and TICP[Psi] (H-Tyr-TicPsi[CH(2)NH]Cha-Phe-OH); Cha: cyclohexylalanine), which are widely used in opioid research. Theoretical conformational analyses in conjunction with the pharmacological characterization of conformationally constrained TIPP analogues led to a definitive model of the receptor-bound conformation of H-Tyr-Tic-(Phe-Phe)-OH-related delta opioid antagonists, which is characterized by all-trans peptide bonds. Further structure-activity studies revealed that the delta antagonist vs delta agonist behavior of TIP(P)-derived compounds depended on very subtle structural differences in diverse locations of the molecule and suggested a delta receptor model involving a number of different inactive receptor conformations. A further outcome of these studies was the identification of a new class of potent and very selective dipeptide delta agonists of the general formula H-Tyr-Tic-NH-X (X = arylalkyl), which are of interest for drug development because of their low molecular weight and lipophilic character. Most interestingly, TIPP analogues containing a C-terminal carboxamide group displayed a mixed mu agonist/delta antagonist profile, and thus were expected to be analgesics with a low propensity to produce tolerance and physical dependence. This turned out to be the case with the TIPP-derived mu agonist/delta antagonist DIPP-NH(2)[Psi] (H-Dmt-TicPsi[CH(2)NH]Phe-Phe-NH(2)); Dmt: 2',6'- dimethyltyrosine).

Models, Molecular↗
PubMed2006

Desensitization of 5-HT(1A) autoreceptors induced by neonatal DSP-4 treatment.

To examine the effect of noradrenergic lesion on the reactivity of central 5-HT(1A) receptors, DSP-4 (50 mg/kg) was administered neonatally 30 min after zimelidine (10 mg/kg) administration. 5-HT(1A) autoreceptors are involved in the regulation of serotonin (5-HT) synthesis. In HPLC assay R-(+)-8-OH-DPAT (0.03 mg/kg) significantly decreased 5-HT synthesis rate in striatum, hypothalamus and frontal cortex of control, whilst nonsignificantly in DSP-4-lesioned adult rats (10-12 weeks old). To determine which type of receptor, pre- or postsynaptically located, is involved in the attenuated response to 5-HT(1A) receptors' agonist, behavioral tests were conducted. R-(+)-8-OH-DPAT (0.015 mg/kg) caused hyperphagia of control rats, but did not change feeding of DSP-4 treated rats. R-(+)-8-OH-DPAT (0.1 mg/kg) induced hypothermia and "5-HT(1A) syndrome" in both control and DSP-4-lesioned animals. The nature of this phenomenon is attributable to the presynaptic adaptive mechanism and suggests the desensitization of 5-HT(1A) autoreceptors of rats with neonatal lesion of the central noradrenergic system.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Urine marking and maternal aggression of wild female mice in relation to anogenital distance at birth.

A series of experiments were conducted with wild house mice to verify the effect of intrauterine position on females' anogenital distance at birth (AGD) and to examine the relationships between a female's AGD, used as a bioassay of androgen exposure during fetal life, and her social behavior and reproductive success in adulthood. Experiment 1 showed that cesarean-delivered females that developed in utero between two males (2 M females) have significantly longer AGD's than females positioned between two females (0 M females). We then categorized naturally delivered females shortly after birth as having a long, medium or short AGD. In adulthood, these females were tested for their behavior towards unfamiliar pups, their rate of urine-marking in response to a variety of social stimuli, postpartum aggression and success in protecting their litters in response to male and female intruders. Adult females with different AGD's at birth did not differ either in their behavior toward pups or in their rate of urine marking. Conversely, males housed across a wire mesh partition from a long-AGD female deposited a higher number of urine marks than those exposed to a short-AGD female. When tested after delivering a litter, long-AGD females displayed more tail-rattling (a component of agonistic behavior) towards intruders of both sexes in comparison to short-AGD females. These results are consistent with the hypothesis that females with a long AGD are exposed to higher levels of Testosterone during fetal life than females with a short AGD. Although not related to AGD, other measures of maternal aggression were affected by postpartum day, sex of intruders and a female's infanticidal potential while a virgin.

Aggression↗
PubMed2004

Digit length ratios predict reactive aggression in women, but not in men.

Considerable evidence suggests that digit length and dermatoglyphic asymmetry patterns in the hand are affected by early exposure to androgens. Because androgens play an important role in sexual differentiation of morphological and behavioral traits, digit length patterns often display sex differences. When present, sex differences in digit lengths are more pronounced on the right side as compared to the left side. Moreover, the ratio of the second to fourth digit length (2D:4D) in the right hand is inversely correlated with testosterone (T) in men. Because T is implicated in agonistic behavior, 2D:4D may be used as a marker of androgen exposure and subsequent behavioral variation in adulthood. Consequently, we investigated the relationships among 2D:4D, directional asymmetry of 2D:4D (left hand 2D:4D minus right hand 2D:4D) as a variant of T, and human reactive aggression. One hundred young men (n = 51) and women (n = 49) participated in our experiments (mean age = 20.1 years). Participants called two noncompliant confederates to solicit donations for a fictitious charity organization and selected follow-up letters after the calls. The force exerted when hanging up the phone and the "tone" of the follow-up letters were used to assess reactive aggression. High aggression scores were associated with high directional asymmetry of 2D:4D and masculinized (low) right hand 2D:4D, only in females and under high provocation. Directional asymmetry of 2D:4D was positively correlated with T in males (pooled data, n = 97). Taken together, these data confirm the predominantly right-sided influence of androgens on digit length and suggest that digit length ratios may be associated with female reactive aggression when sufficient provocation is present.

Adult↗
PubMed1981

Analysis of amphetamine effects on agonistic and affiliative behavior in squirrel monkeys (Saimiri sciureus).

Two series of experiments were performed to differentiate the effects of d-amphetamine on social interactions from those on solitary motor behavior in adult and juvenile squirrel monkeys. In the first experiment, d-amphetamine (3x0.5 mg/kg, PO) induced pronounced stereotyped movements of the head, limbs and torso. When confronted in the colony room with an intruder monkey, the amphetamine-treated resident monkey showed reduced threat and attack behavior. In a separate test for affiliation, amphetamine nearly abolished the affiliative response toward a familiar group member. In a second series of experiments, d-amphetamine (0.3, 1.0 mg/kg, IM) decreased the affiliative behavior of juvenile monkeys towards their mothers; yet, in the presence of an unfamiliar adult male, the detrimental effect of amphetamine on affiliative behavior was prevented. Morphine (0.5, 2.0 mg/kg) increased the affiliative response toward the mother, and chlordiazepoxide (5, 10 mg/kg) was without effect in this situation. These observations suggest that amphetamine impairs a range of social behavior in adult and juvenile monkeys. The general disruption of agonistic and affiliative behaviors due to amphetamine appears to be based on mechanisms which differ from those mediating stereotyped movements. Stimulant-induced changes in social interactions in primates may be linked to disturbed affect.

Amphetamine↗
PubMed2006

Psychosocial stress alters ethanol's effect on open field behaviors.

Psychosocial stress, including social rank status, has been shown to alter spontaneously occurring behaviors in rodents as well as the behavioral effects of drugs of abuse. In this study, rats were repeatedly evaluated in a modified open field following: their initial exposure, and after intraperitoneal injections of saline and 0.75 g/kg ethanol (EtOH). All subjects were first tested while under single housing conditions, then again following 35 days of differential housing (singly or 3 rats/cage) with social status determined by scoring agonistic behavior at triad formation. The data suggest that (1) future subordinate rats differed with respect to specific aspects of behavior displayed in a 'novel' open field arena, (2) future subordinate rats were more emotional since they showed greater "anxiety-like" behavior and less exploratory behavior, (3) subordinate rats were more impaired by the saline injection stress, (4) subordinate rats were more sensitive to the depressant effects of EtOH, (5) grooming behavior did not show habituation, in contrast to the other behaviors, but showed sensitization on the second test. Overall, subordinate rats may have differed from their cage mates in innate anxiety, and this may underlie their distinct response to both stressors and EtOH. Furthermore, while EtOH had mostly stimulant effects in naive rats, psychosocial stress and/or repeated testing resulted in enhancement of EtOH's depressant effects.

Animals↗
PubMed2006

Social lives of adult Mysore slender lorises (Loris lydekkerianus lydekkerianus).

Despite the persistent use of the word "solitary" to describe nocturnal primate social behavior, increasing numbers of studies are revealing sophisticated levels of social interactions among nocturnal primates. This study explores the relationships among 11 adult Mysore slender lorises (Loris lydekkerianus lydekkerianus) studied over 10(1/2) months in Tamil Nadu, India. When all observations regarding dependent offspring are excluded, the animals spent on average 38% of their activity in various forms of neutral, affiliative, and agonistic behaviors. Affiliative behaviors were the most common type of social interaction, and males in general were more social than females. Low values for Cole's index (CI) of association emphasize that females rarely interacted with same-sex conspecifics, but commonly interacted with males. In turn, males also formed strong affiliative relationships with other adult males. This index also indicates that levels of affiliation are strongest among animals that share sleeping sites. The Hinde index (HI) suggests that males control proximity to females more than the reverse. A female's tolerance of multiple males in her home range and at a sleeping site may be related to high spatial variability of food resources. Such resources may constrain females with costly reproductive strategies (up to two sets of twins per annum) to a small home range. With their larger home ranges, males may be able to monopolize females by initiating social interactions, and also provide a benefit to females by contributing to parental care.

Animals↗
PubMed1995

Physiological substrates of mammalian monogamy: the prairie vole model.

Prairie voles (Microtus ochrogaster) are described here as a model system in which it is possible to examine, within the context of natural history, the proximate processes regulating the social and reproductive behaviors that characterize a monogamous social system. Neuropeptides, including oxytocin and vasopressin, and the adrenal glucocorticoid, corticosterone, have been implicated in the neural regulation of partner preferences, and in the male, vasopressin has been implicated in the induction of selective aggression toward strangers. We hypothesize here that interactions among oxytocin, vasopressin and glucocorticoids could provide substrates for dynamic changes in social and agonistic behaviors, including those required in the development and expression of monogamy. Results from research with voles suggest that the behaviors characteristics of monogamy, including social attachments and biparental care, may be modified by hormones during development and may be regulated by different mechanisms in males and females.

Animals↗