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PubMedDate not supplied

Chronic social stress, social status, and susceptibility to upper respiratory infections in nonhuman primates.

OBJECTIVE: The objective of the study was to assess the roles of social stress and social status in susceptibility to upper respiratory infection. METHOD: Sixty male cynomolgus monkeys were randomly assigned to stable or unstable social conditions for 15 months. Two markers of social status, social rank and percent of behaviors that were submissive, were assessed at independent observation periods. Endocrine, immune, and behavioral responses were each assessed (at 3-month intervals) during the 9th through 14th months of the study. At the beginning of the 15th month, all animals were exposed to a virus (adenovirus) that causes a common-cold-like illness. The primary outcome was whether or not an animal developed an infection (shed virus) after viral exposure. RESULTS: Although the social instability manipulation was associated with increased agonistic behavior as indicated by minor injuries and elevated norepinephrine responses to social reorganizations, the manipulation did not influence the probability of being infected by the virus. However, low social status (as assessed by either marker) was associated with a substantially greater probability of being infected. It was also associated with less body weight, greater elevated cortisol responses to social reorganizations, and less aggressive behavior. However, none of these characteristics could account for the relation between social status and infection. CONCLUSIONS: Social stress was not associated with susceptibility to infection. However, animals with lower social status were at higher risk than high social status animals.

Adenoviruses, Simian↗
PubMed1995

Dopamine receptor subtype agonists and feeding behavior.

Stimulation or blockade of various dopamine receptor subtypes is associated with reduced feeding. For example, D2 receptor agonists suppress feeding in food-deprived and free-feeding rats, and in rats given access to a highly palatable diet. Similarly, reduced food intake is associated with the actions of diverse D1 receptor agonists, and these compounds can interact synergistically with D2 receptor agonists to potentiate reductions in feeding. Using microstructural analysis to compare D1 and D2 agonist effects, specific differences emerge in their modes of action. D1 agonists reduce the duration of feeding, primarily by decreasing the frequency of feeding bouts, whereas D2 agonists reduce the local rate of eating. However, since D1 agonists uniquely reduce feeding in the absence of other behavioral impairments and are less disruptive of the pattern of feeding behavior, it has been suggested that D1 agonists are more likely than D2 agonists to act on central mechanisms regulating food intake. Moreover, only D1 agonists are effective in suppressing sucrose sham-feeding, suggesting that D1 receptor stimulation may promote satiety. Nevertheless, many questions remain. For example, antagonist studies have implicated 5-HT receptor stimulation in the anorectic effects of D1 agonists, suggesting that further pharmacological and behavioral analyses of receptor-subtype agonist effects are required. Above all, recent developments in the classification of dopamine receptor subtypes reveal the need for new studies examining the involvement of D3, D4 and D5 receptors in feeding.

Animals↗
PubMed1990

Oral contraceptive administration, interfemale relationships, and sexual behavior in Macaca fascicularis.

The effects of oral contraceptive administration on the social relationships of adult female cynomolgus monkeys (Macaca fascicularis) were examined. Ten females were administered ethinyl estradiol/ethynodiol diacetate (Demulen), 10 were administered ethinyl estradiol/norgestrel (Ovral), and 10 served as a control group. The monkeys lived in social groups of 5 females each, and patterns of social interaction and social status were recorded. Interfemale relationships were also observed when a vasectomized male was placed in each social group for 50 min, once/week. During the latter observations, preliminary data on the effects of oral contraceptive treatment on sexual interaction were also collected. In the absence of the male, interfemale agonistic interactions and time spent alone were influenced by social status but not by oral contraceptive treatment. Time spent in passive body contact, an affiliative state, was reduced by Ovral treatment. In the presence of the male, dominant females aggressively interfered with the sexual interactions of subordinates. This aggression resulted in the termination of a greater proportion of the sexual interactions of subordinates than dominants in the control group only, indicating suppression of this type of interaction by oral contraceptive treatment. Other effects included a decreased frequency of ejaculation with Ovral-treated females. These results suggest that oral contraceptives may suppress certain types of female agonistic behavior (e.g., in the context of mate competition) and some oral contraceptives may interfere with sexual activity. More broadly, these findings indicate that intrasexual competition for access to mates may occur in females as well as males.

Aggression↗
PubMed1989

Molecular determinants of benzodiazepine receptor affinities and anticonvulsant activities.

In vivo convulsant activities profiles and receptor binding studies together with the techniques of theoretical chemistry were used to characterize 15 compounds, from five different chemical families, known to bind to the BDZ receptor. The experimental goals of this study were to determine the affinity of these analogs for this receptor, the effect of gamma-aminobutyric acid on the affinity, and, in a self-consistent manner, the nature of the activity, agonist (anticonvulsant), antagonist, or inverse agonist (proconvulsant, convulsant), elicited by binding to this receptor. To these ends, in vivo studies were made to determine the proconvulsant, convulsant, and anticonvulsant activities and antagonism to anticonvulsant activities of the 15 analogs. Their receptor affinities at 25 degrees were also determined by competitive inhibition of [3H] flunitrazepam and [3H]Ro 15-1788 in the absence and presence of gamma-aminobutyric acid. The goal of the theoretical studies was to identify and calculate molecular properties that modulate these affinities and types of activities and from them to develop a model of receptor recognition and activation that could consistently explain observed behavior and predict new results. Thus, molecular orbital calculations were carried out for all analogs, using semiempirical quantum mechanical methods. In addition to the optimization of structures, a number of electronic properties, such as polarizations, partition coefficients, and proton and electron affinities were computed and examined for their ability to modulate relative affinities and modes of activation of the receptor. From these studies, a model for receptor recognition involving two anchoring hydrogen bond-acceptor sites and for activation involving interaction of the most lipophilic aromatic region of each compound with the receptor was developed, which could systematically account for the three different types of behavior, agonist, antagonist, and inverse agonist, observed for these analogs. Electronic rather than structural properties were found to be the principal modulator of both recognition and activation. A possible mechanism of agonist activation of the receptor involving electron transfer to the agonist, as well as a possible induced conformational change in the receptor, is also suggested by these results. Finally, by complementarity, some steric and electronic characteristics of the receptor binding site could be deduced.

Animals↗
PubMed1994

Effects of SUN 8399, a potent and selective 5-HT1A agonist, on conflict behavior and ambulatory activity in mice: comparison with those of buspirone, tandospirone and diazepam.

Behavioral effects of p.o. administration of SUN 8399, a selective 5-HT1A agonist, on the operant behavior under a MULT VI 1.5 min/FR 5-punishment schedule of food reinforcement and on the ambulatory activity were evaluated in mice, and the characteristics were compared with those of other 5-HT1A agonists, buspirone and tandospirone, and the benzodiazepine diazepam. Diazepam (3 and 10 mg/kg) significantly increased the punished response without eliciting any significant change in the non-punished response; i.e., showing anticonflict action. SUN 8399 (3-30 mg/kg) and buspirone (1-10 mg/kg) did not significantly change either the punished or non-punished responses. Tandospirone significantly increased the non-punished response at 10 mg/kg, but significantly decreased both the punished and non-punished responses at 30 mg/kg. The single administration of SUN 8399 (10 mg/kg), buspirone (3 and 30 mg/kg) and tandospirone (10 and 30 mg/kg) significantly increased the ambulatory activity, while diazepam tended to decrease it. The ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was reduced by buspirone (10 and 30 mg/kg) and tandospirone (10 and 30 mg/kg), but enhanced by diazepam (3 and 10 mg/kg). Buspirone (30 mg/kg), tandospirone (10 and 30 mg/kg) and diazepam (3 and 10 mg/kg) significantly reduced the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.). SUN 8399 (3-100 mg/kg) did not modify the effects of either methamphetamine or scopolamine. The present results suggest that 5-HT1A agonists scarcely show anticonflict action on the Geller-type conflict behavior in mice. However, SUN 8399 possesses different behavioral characteristics from those of the other two 5-HT1A agonists in terms of interactions with methamphetamine and scopolamine.

Animals↗
PubMed1992

Differential coupling of 5-HT1A receptors occupied by 5-HT or 8-OH-DPAT to adenylyl cyclase.

Human serotonin (5-hydroxytryptamine, 5-HT)-1A receptors have been transfected in NIH-3T3 cells, and their coupling to adenylyl cyclase was analysed depending on 1) the number of receptor expressed, 2) the experimental conditions used, 3) the nature of the agonists. Two monoclonal cell lines were used, expressing low (45 fmol/mg) and high (500 fmol/mg) levels of 5-HT1A receptor. Two methods were tested to study the negative coupling of the transfected 5-HT1A receptors to adenylyl cyclase: 1) measurement of cAMP production in intact cells, 2) measurement of adenylyl cyclase activity in vitro on membrane preparations. Studies on intact cells revealed that an increase in the receptor concentration was followed by 1) an increase in the efficacies of 5-HT, 5-CT (5-carboxamidotryptamine) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 2) a 2 to 3-fold increase in the potency of 5-CT and 8-OH-DPAT, but no change in the potency of 5-HT. In membrane preparations, 8-OH-DPAT dose-response curve was shifted leftwards when the receptor concentration became higher whereas the corresponding shift was smaller for 5-HT and absent for 5-CT. Surprisingly, on membrane preparations, 8-OH-DPAT was a partial agonist relative to 5-HT. The relative efficacy of 8-OH-DPAT was lower in the clone expressing the lowest level of receptor. This partial agonist behavior of 8-OH-DPAT could be modulated by the ionic conditions under which the adenylyl cyclase activity was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2006

Analgesic activity of a non-peptide imidazolidinedione somatostatin agonist: in vitro and in vivo studies in rat.

Several lines of evidence support an important role for somatostatin receptors (SSTRs) in pain modulation. The therapeutic use of established SSTR peptide agonists for this indication is limited by their broad range of effects, need for intrathecal delivery, and short half-life. Therefore, the goal of the present study was to investigate the analgesic effect of SCR007, a new, highly selective SSTR2 non-peptide agonist. Behavioral studies demonstrated that paw withdrawal latencies to heat were significantly increased following intraplantar SCR007. Furthermore, both intraperitoneal and intraplantar injection of SCR007 significantly reduced formalin- and capsaicin-induced flinching and lifting/licking nociceptive behaviors. Recordings from nociceptors using an in vitro glabrous skin-nerve preparation showed that SCR007 reduced heat responses in a dose-dependent fashion, bradykinin-induced excitation, heat sensitization and capsaicin-induced excitation. In both the behavioral and single fiber studies, the SCR007 effects were reversed by the SSTR antagonist cyclo-somatostatin, demonstrating receptor specificity. In the single fiber studies, the opioid antagonist naloxone did not reverse SCR007-induced anti-nociception suggesting that SCR007 did not exert its effects through activation of opioid receptors. Analysis of cAMP/protein kinase A (PKA) involvement demonstrated that SCR007 prevented forskolin- and Sp-8-Br-cAMPS (a PKA activator)-induced heat sensitization, supporting the hypothesis that SCR007-induced inhibition could involve a down-regulation of the cAMP/PKA pathway. These data provide several lines of evidence that the non-peptide imidazolidinedione SSTR2 agonist SCR007 is a promising anti-nociceptive and analgesic agent for the treatment of pain of peripheral and/or central origin.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Risk to tourists posed by wild mammals in South Africa.

BACKGROUND: One of South Africa's principal tourist attractions is the opportunity to encounter Africa's large mammals in the wild. Attacks by these mammals can be exceptionally newsworthy with potentially deleterious effects on tourism. Little is known about the risk of injury and death caused by wild mammals to visitors to South Africa's nature reserves. The aim of this study was to determine the incidence of fatal and nonfatal attacks on tourists by wild mammals in South Africa and to ascertain avoidable factors, if any. METHODS: Commercial press records covering all South African Newspapers archived at the Independent Newspapers' central library were systematically reviewed for a 10-year period, January 1988 to December 1997 inclusive, to identify all deaths and injuries to domestic and international tourists resulting from encounters with wild mammals in South Africa. All of these incidents were analyzed to ascertain avoidable factors. RESULTS: During the review period seven tourists, including two students from Thailand and a German traveler, were killed by wild mammals in South Africa. Three of the four deaths ascribed to lions resulted from tourists carelessly approaching prides on foot in lion reserves. A judicial inquiry found that the management of a KwaZulu-Natal Reserve was culpable for the remaining death. Tourist ignorance of animal behavior and flagrant disregard of rules contributed to the two fatalities involving hippopotami. The unusual behavior manifested by the bull elephant responsible for the final death, resulted from discomfort caused by a dental problem to this pachyderm. During the same period there were 14 nonfatal attacks on tourists, including five by hippo, three by buffalo, two by rhino, and one each by a lion, leopard, zebra and musth elephant. Only the latter occurred while the visitor was in a motor vehicle. Tourist ethological naivete and failure to determine the experience of trail guides prior to travel, resulted in inadvertent agonistic behavior, unnecessary risk-taking and avoidable injury. CONCLUSIONS: This retrospective study has shown that attacks on tourists by wild mammals in South Africa are an uncommon cause of injury and death. Sensible precautions to minimize this risk include remaining in a secure motor vehicle or adequately fenced precincts while in the vicinity of large mammals, rigidly observing nature reserve instructions, never approaching animals that appear ill, malnourished, displaying aggressive behavior traits or female wild mammals with young, and demanding adequately trained and experienced game rangers when embarking on walking trails. Any behavior that might be construed as antagonistic and which could provoke an attack by large mammals should be avoided (e.g., driving directly at a lion). Visitors need to be informed of classic signs of aggression, in particular in elephants, which will allow timely avoidance measures to be taken. The risk-enhancing effect of excessive alcohol intake is undesirable in the game reserve setting, as is driving at high speed after dusk in areas where hippos graze. Local advice on personal safety in wildlife reserves and the credentials of trail guides should be obtained from lodge or reserve management, tourism authorities or the travel industry prior to travel to game reserves.

Adolescent↗
PubMed1983

Behavior and performance of pigs grouped by three different methods at weaning.

Crossbred pigs (384) used in three trials were assigned to one of three grouping treatments when moved to 1.4 X 1.6 m nursery pens 4 h postweaning at 28 d of age. Treatments included eight pigs from the same litter (8-1), four pigs from each of two different litters (4-2) and one pig from each of eight different litters (1-8). A commercial odor masking agent (OMA) commonly used to reduce tail biting and fighting was sprayed on one-half of the replicates of each treatment 20 min after (trial 1) or immediately before (trials 2 and 3) the pigs were moved to the nursery. Agonistic behavior was quantified (trials 2 and 3) by direct observation for the first 3 h and again for 2 h at 24 and 48 h post-grouping. Application of OMA 20 min post-mixing caused only a temporary (3 to 5 min) cessation of fighting. A slight increase in fighting in all three grouping treatments was observed when OMA was applied before mixing. Average daily gain for 0 to 4 and 0 to 28 d and feed intake for 0 to 7 and 0 to 28 d were not influenced by OMA or grouping treatments. Combining alien pigs resulted in a significant increase in fighting but did not affect long term performance.

Animals↗
PubMed1976

Effects of Sevin on the reproductive biology of the Coturnix.

Adult Coturnix quail (Coturnix coturnix japonica) were subjected to three levels of carbaryl pesticide treatment (Sevin-20 p.p.m., 40 p.p.m., and 400 p.p.m) and monitored to observe any modifications in either their reproductive biology or behavior. There was an increase in the amount of pesticide excreted with increasing treatment levels during the first 48 hours following intubation, after which pesticide levels in the fecal material for all groups approached zero. Addditionally, significant amounts of the pesticide were detected in the egg yolks after pesticide ingestion (treatment levels, 20, 40, and 400 p.p.m. resulted in pesticide residues of 1.58, 2.03, and 3.15 p.p.m., respectively). Egg production was significantly reduced (p less than or equal to 0.05), although egg viability was not affected by the pesticide stress. Agonistic behavior decreased in males while it increased in the females following pesticide ingestion.

Aggression↗
PubMed1993

Season affects tolerance of cohabitation by deer mice.

We measured the resting metabolic rates of Peromyscus maniculatus for 7 days before and 7 days following forced pairing in order to determine whether seasonal light cycles influenced the rates of behavioral and metabolic habituation of deer mice to cohabitation. We had earlier shown that winter photoperiod and/or huddling results in lower resting metabolic rates and core temperatures of deer mice. Seasonal photoperiods were simulated by conditioning wild-caught mice to 24-h light cycles with differing durations of light exposure during the 24 h day. These experiments demonstrated that winter mice adjusted their resting metabolic rates from solitary to huddling levels much more rapidly than summer mice. Initial, high metabolic rate responses of paired mice persisted much longer than expressions of agonistic behaviors between paired mice. We propose that winter photoperiod enables animals to more efficiently make the transition to spontaneous, amicable huddling as a winter acclimatization strategy.

Animals↗
PubMed1991

Lead effects on food competition and predatory aggression in Binghamton HET mice.

The ubiquity of lead in our environment, its toxic nature and its potential to alter behavior of humans and animals has stimulated much research. In addition to the well known, but complex, changes in activity and performance of learned tasks following exposure to lead, an increasing body of literature suggests that changes in social behavior also occur. This study examined the impact of ingesting a 0.5% lead acetate solution (as the only available fluid)--a protocol that results in ca. 100 micrograms/dl blood-levels in our Binghamton Heterogenous (HET) mice--on food competition in both male and female HET mice. Effects of this lead exposure on cricket predation by the same HET mice also were observed. Our results from the food competition study (Experiment I) show, compared with water controls, that such exposure to lead increases both food possession time and amount of social contact after food consumption; but very little agonistic behavior took place in either the water control or lead-exposed competition testing sessions. In the cricket predation observations (Experiment II) there was a tendency for lead exposure to reduce the latency of males to attack, and the indication that lead-exposed females initially attacked a cricket's legs more often than any of the other groups. In fact, suggestions of such gender x treatment interactions occurred in both the food competition and the predation work. Overall, we believe our results, in conjunction with other relevant literature, suggest that exposure to lead reduced the individual's general fitness, even when levels are relatively low.

Aggression↗
PubMed2006

3-Hydroxy-2-butanone and the first encounter fight in the male lobster cockroach, Nauphoeta cinerea.

Although agonistic behavior in the male lobster cockroach, Nauphoeta cinerea, has been known for more than 40 years, this is the first study to directly collect and quantify the emitted pheromones. In the present study, emitted volatile pheromones were collected from each male pair for 60 min during the first encounter fight and identified and quantified by gas chromatography-mass spectrometry. The major compound collected was 3-hydroxy-2-butanone (3H-2B). The strength of the attack by the dominant male was classified into three categories from weakest (C) to strongest (A). Of the 92 pairs, eight (8.7%) showed no agonistic interactions, and the amount of 3H-2B collected was 121.8+/-37.7 ng/male pair. In the five pairs (5.4%) displaying attack strength C, the amount of 3H-2B collected was 689.6+/-273.7 ng/male pair, and the attack duration was 9.6+/-2.4 min. In the 53 pairs (57.6%) showing attack strength B, the corresponding values were 5396.2+/-449.0 ng/male pair and 22.7+/-1.6 min, while those for the 26 pairs (28.3%) showing attack strength A were 7910.4+/-1120.6 ng/male pair and 24.9+/-2.9 min. For both attack strengths A and B, a linear relationship was found between the amount of 3H-2B collected and attack duration, suggesting that the longer the duration of the attack, the more 3H-2B was emitted. In addition, the rate of 3H-2B emission for attack strength A was significantly higher than that for attack strength B. Using Vaseline-coating, we demonstrated that, in the first encounter fight, the 3H-2B was emitted by the dominant male.

Acetoin↗
PubMed2002

Synthetic maternal pheromone stimulates feeding behavior and weight gain in weaned pigs.

One hundred and forty-four pigs were used to determine the effects of a putative synthetic maternal pheromone on behavior and performance of weanling pigs. Each pen of weaned pigs contained three pigs that were given free access to water and feed. Pigs were videotaped in time lapse for 48 h after weaning and weekly body weights and feed disappearances were recorded for 4 wk. Treatments included: a) control (vehicle applied), b) 30 mL of synthetic pheromone applied to the feeder, or c) 10 mL of synthetic pheromone applied to each of three pigs' snouts. Pigs exposed to the synthetic pheromone spent more (P < 0.05) time with their heads in the feeder and less (P < 0.05) time drinking, lying down, or engaged in agonistic behaviors than control pigs. Pigs exposed to the synthetic pheromone were more (P < 0.05) active during the 48-h period of video taping than control pigs. Pigs exposed to the synthetic pheromone (either on the feeder or their snout) had increased (P < 0.01) average daily gain (ADG) and better (P < 0.01) feed:gain ratio than control pigs over the 28-d postweaning period. In conclusion, the putative synthetic pheromone, applied once at weaning, stimulated apparent feeding behaviors, and reduced fighting and apparent drinking behaviors during the first 48 h after weaning. ADG and feed:gain ratio were improved by application of the putative synthetic pheromone either directly on the feeder or when painted on the pigs' snouts. Olfactory signals can modulate adaptation to the postweaning environment in ways that may improve pig performance and welfare.

Animals↗
PubMed2006

Maternal aggression persists following lipopolysaccharide-induced activation of the immune system.

Lactating females direct aggressive behaviors towards intruders presumably to reduce the likelihood of infanticide of their pups. Infected animals display a constellation of responses that include lethargy, anorexia, and decreased social interactions. This suite of responses is referred to as sickness behavior, and is putatively part of an adaptive strategy to aid the organism in recovery from infection. Previous work has suggested that animals can suppress the behavioral symptoms of sickness in order to engage in adaptive behaviors. To test whether adaptive nest defense is affected by illness, dams received a peripheral injection of either saline or lipopolysaccharide (LPS [50, 400, or 1000 microg/kg]), a non-replicating component of bacterial cell walls that activates the immune system. Simulated infection with LPS reduced body mass and food intake in dams and interfered with litter growth in a dose-dependent manner. Generally, nest defense was unaffected by LPS; the proportion of dams displaying maternal aggression against a male intruder, as well as the latency and duration of aggressive encounters were only suppressed at the highest LPS dose tested. Further, LPS treatment also altered non-agonistic behavior during the aggression test as indicated by reduced social investigation of the intruder and an increased time spent immobile during the session. LPS administration also significantly increased serum corticosterone concentrations in lactating females. These findings suggest that maternal aggression is not suppressed by LPS-evoked immune activation at doses that attenuate other aspects of maternal and social behavior.

Adaptation, Physiological↗
PubMed2003

Food competition in captive female sooty mangabeys (Cercocebus torquatus atys).

We studied the social and foraging behavior of two captive groups of sooty mangabeys under two different spatial food situations. These food conditions were clumped (food was placed in a box) and dispersed (food was dispersed over the entire enclosure). In each group five adult females and two adult males were observed. As a criterion for food competition, individual differences in the relative food intake were used. Adult female mangabeys had a linear, stable, and unidirectional dominance hierarchy. Access to food was rank dependent among females only under clumped food distribution, as current models of the evolution of primate social systems predict. However, feeding success appeared to be mediated not by female but by male agonistic behavior toward females. High-ranking females received relatively less aggression from males and could, therefore, stay and feed longer in the feeding area. Male tolerance of higher-ranking females seems to mediate female feeding success under restricted food resources. The establishment of a special relationship with a high-ranking male might, therefore, be a strategy to get better access to food. This study demonstrates that female competition for access to food should not be analyzed separately from male influences on females and suggests that a more integral role of males in socioecological models of the evolution of primate social systems should be considered.

Animals↗
PubMed1997

The Caenorhabditis elegans seven-transmembrane protein ODR-10 functions as an odorant receptor in mammalian cells.

The nematode Caenorhabditis elegans exhibits behavioral responses to many volatile odorants. Chemotaxis toward one such odorant, diacetyl (butanedione), requires the function of a seven-transmembrane receptor protein encoded by the odr-10 gene. To determine directly whether ODR-10 protein is an odorant receptor, it is necessary to express the protein in a heterologous system and show that it responds to diacetyl by activation of a G protein signaling pathway. Here we demonstrate that human cells expressing ODR-10 on their surfaces exhibit a transient elevation in intracellular Ca2+ levels after diacetyl application. Volatile compounds that differ from diacetyl only by the addition of a methyl group (2,3-pentanedione) or the absence of a keto group (butanone) are not ODR-10 agonists. Behavioral responses to these compounds are not dependent on odr-10 function, so ODR-10 specificity in human cells resembles in vivo specificity. The apparent affinity of ODR-10 for diacetyl observed in human cells is consistent with the diacetyl concentration ranges that allow efficient nematode chemotaxis. ODR-10 expressed in human cells also responds to two anionic compounds, pyruvate and citrate, which are metabolic precursors used for diacetyl production by certain bacterial species. Ca2+ elevation in response to ODR-10 activation is due to release from intracellular stores.

Animals↗
PubMed1992

Central monoaminergic mechanisms in mice and analgesic activity of spiradoline mesylate, a selective kappa-opioid receptor agonist.

We assessed the roles of brain monoaminergic systems in the analgesic action of spiradoline, a novel kappa-opioid agonist, behaviorally and biochemically by using noradrenaline (NE) and serotonin (5-HT) uptake inhibitors. Analgesic activity was evaluated by measuring latency time in the mouse tail-pinch test. Spiradoline at intramuscular doses of 0.3 mg/kg or more elicited a significant analgesic effect and the metabolism of both NE and 5-HT was significantly increased in brainstem and cortex. Pretreatment of the mice with imipramine, desipramine or clomipramine caused marked potentiation of spiradoline analgesia, whereas reserpine and phenoxybenzamine inhibited it. Morphine analgesia was enhanced by clomipramine but not by imipramine, desipramine or phenoxybenzamine. These results suggest that excitation of noradrenergic and serotonergic pathways in the brain appears to be involved in spiradoline analgesia, and that, as regards tail-pinch nociception, the kappa-opioid agonist acts on the noradrenergic pathway more potently than morphine.

Analgesics↗