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PubMed2000

In vivo characterization of novel full and partial 2-(4-aminophenyl)-N,N-dipropylethylamine dopamine D(2) receptor agonists.

Behavioral and biochemical techniques were used to compare the in vivo intrinsic efficacy of two new 2-(4-aminophenyl)-N, N-dipropylethylamine dopamine D(2) receptor agonists, 2-(4-amino-3-trifluoromethylphenyl)-N-N-dipropyl-ethylamine (NBF-203) and 2-(4-amino-3-bromo-5-trifluoromethylphenyl)-N-N-dipropylethylamine (NBF-234). Adult male Sprague-Dawley rats were used as experimental animals. NBF-203 was characterized as a full dopamine D(2) receptor agonist, whereas NBF-234 displayed properties of a partial agonist, or antagonist, at dopamine D(2) receptors. Thus, NBF-203 produced effects similar to those of apomorphine in models for dopamine synthesis, release and turnover. As a strong indication of markedly less intrinsic efficacy, the administration of NBF-234 did not result in antagonism of reserpine-induced suppression of locomotor activity in the presence of (+/-)-1-phenyl-2,3,4,5, -tetrahydro-(1H)-3-benzazepine-7,8-diol HCl (SKF-38393)-induced dopamine D(1) receptor activation. The present series of compounds offer the possibility of adjusting intrinsic efficacy at dopamine D(2) receptors, and such fine-tuning could be an important strategy in the search for optimal antipsychotic or antiparkinson drugs within the partial dopamine D(2) receptor agonist concept.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

Effects of amperozide on biting behavior and performance in restricted-fed pigs following regrouping.

Eight experiments were conducted to determine the effect of a single administration of amperozide on agonistic behavior and growth performance in newly mixed, restricted-fed pigs. Two hundred 12-wk-old pigs were used in a 4-wk trial (Exp. 1) to investigate the effect of amperozide on agonistic behavior and performance. The pigs were assigned to each pen on the basis of body weight and sex, ensuring that pigs in each pen were unacquainted. Each pig was weighed individually on d 3, 7 and 28. Agonistic behavior was quantified by counting bite and slash marks on each pig at 8, 26 and 48 h after penning. An i.m. injection of amperozide immediately before mixing the pigs reduced the physical damage (P less than .001) at each time point. There was no evidence of amperozide causing either sedation or motor disturbances. On the average, amperozide treatment improved (P less than .001) daily gain in the 4-wk study period by 70 g (17%). In Exp. 2 to 8, 1,648 pigs growing from approximately 20 to 100 kg body weight were used to determine the effect of amperozide on weight gain. Pigs were penned in groups of 9 to 11, randomly assigned to each pen on the basis of sex. Each pig was weighed individually after penning, on d 35 and at slaughter. Untreated control pigs had a poorer growth performance than did amperozide-treated pigs. During the first 5 wk postpenning average daily gain was improved (P less than .001) by 90 g (26%) in pigs receiving a single oral administration of amperozide at penning.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗
PubMed2007

Effects of two types and two genre of music on social behavior in captive chimpanzees (Pan troglodytes).

Is music just noise, and thus potentially harmful to laboratory animals, or can it have a beneficial effect? Research addressing this question has generated mixed results, perhaps because of the different types and styles of music used across various studies. The purpose of this study was to test the effects of 2 different types (vocal versus instrumental) and 2 genres (classical vocal versus 'easy-listening' vocal) of music on social behavior in 31 female and 26 male chimpanzees (Pan troglodytes). Results indicated that instrumental music was more effective at increasing affiliative behavior in both male and female chimpanzees, whereas vocal music was more effective at decreasing agonistic behavior. A comparison of 2 genre of vocal music indicated that easy-listening (slower tempo) vocal music was more effective at decreasing agonistic behavior in male chimpanzees than classical (faster tempo) vocal music. Agonistic behavior in females remained low (<0.5%) throughout the study and was unaffected by music. These results indicate that, like humans, captive chimpanzees react differently to various types and genres of music. The reactions varied depending on both the sex of the subject and the type of social behavior examined. Management programs should consider both type and genre when implementing a musical enrichment program for nonhuman primates.

Animals↗
PubMed1999

Lack of effect of the 5-HT(1A) receptor antagonist WAY-100635 on murine agonistic behaviour.

The present study examined the influences of the selective 5-HT1A receptor antagonist, WAY-100635, on the social and agonistic behavior exhibited by male resident mice during encounters with unfamiliar intruder conspecifics. Acute administration of WAY-100635 (0.01-1.0 mg/kg sc) dose dependently enhanced the duration of resident maintenance behavior, reaching statistical significance at 1.0 mg/kg. The duration of resident attend/approach behavior was reduced at 0.01 mg/kg. Drug-free intruder animals showed a reduction in the frequency and duration of attend/approach behavior when the resident mice were treated with 0.01 mg/kg WAY-100635. No other significant effects on behavior were detected for WAY-100635. A previous investigation reported that WAY-100635 induced anxiolytic-like effects in the mouse light/dark box test. In the present study, however, the level of defensive behavior of the saline-treated resident mice was too low for any further anxiolytic-like attenuation of this behavior to be observed. Therefore, no conclusions regarding the potential anxiolytic activity of WAY-100635 may be drawn from the data presented here. Current results are consistent with data for the lack of effect of WAY-100635 on rat agonistic behavior but contrast with findings for the effects of the 5-HT1A receptor antagonists (+)-WAY-100135 and SDZ 216-525 on mouse agonistic behavior.

Agonistic Behavior↗
PubMed2004

A non-social and isolate rearing condition induces an irreversible shift toward continued fights in the male fighting fish (Betta splendens).

Effects of rearing conditions were examined in the development of agonistic behaviors in the male fighting fish. In group-I (highly social), fish were communally reared. In group-II (highly social and isolate), fish were individually housed and exposed to the group-I fish through transparent walls until the sexual maturity (from 6 to 12 weeks post-hatch). In group-III (social and isolate), individually housed fish were similarly exposed to other fish within the group. In group-IV (non-social and isolate), individually housed fish were further visually isolated. Agonisitc behaviors were compared among males of the groups-II, -III, and -IV in their fights against the group-I male. The group-IV males showed significantly higher rate of wins than the groups-II and -III males, without differences in the incidence of agonistic behaviors (butt-or-bite, chase, and gill-cover erect) before the termination of the mutual fights. Increased incidence of agonistic behaviors was found after the termination (particularly in the unilateral chase), suggesting that the group-IV males continued to fight even after the opponent male displayed a submission. The aggression was also enhanced in the group-II, when they were thereafter reared in a social isolation after the sexual maturation; a critical period was thus not found. The enhanced aggression was not reversed in the group-IV, when they were thereafter exposed to social stimuli; shift to the continued fights was irreversible. Possible fitness gain of the enhanced aggression was discussed in terms of the adjustability to altered biological resources.

Agonistic Behavior↗
PubMed1988

Repeated tests of intermale aggression in mice (Mus musculus) are influenced by housing and test conditions.

Young adult male Binghamton Heterogenous (HET) mice were housed either individually or in groups of four, in two-tiered cages for 11 days before their agonistic behavior was observed. Pairs of male mice were tested 3 min each day for 9 consecutive days. Agonistic behavior was observed in two-tiered cages in which there were either clean pine shavings or shavings soiled by young adult female HET mice. Housing and shaving conditions interactively influenced aggression observed over the course of testing. That is, when individually housed mice were tested with clean shavings and when group-housed mice were tested with female-soiled shavings, agonistic behavior decreased over days, but when isolated mice were tested in soiled shavings and when group-housed mice were tested in clean shavings, aggression increased over the course of the 9-day test period.

Aggression↗
PubMed1979

Morphine withdrawal induced behavior in the Syrian hamster (Mesocricetus auratus).

The effects of morphine withdrawal on a number of behaviors was assessed using a design varying sex, amount of morphine implanted, degree of dependence at the time of testing and amount of morphine antagonist injected. Increases in two types of agonistic behavior were seen and may be related to the aversive interoceptive stimuli associated with withdrawal. Furthermore, correlations for males were found between agonistic behavior and activity, wet shakes, digging and vocalization. Agonistic behavior was correlated only with activity in females.

Animals↗
PubMed1976

Selection for agonistic begavior in wild female Mus musculus.

Artificial selection was used to establish different levels of agonistic behavior in laboratory-reared wild female Mus musculus. A within-family selection design with replicated high and low lines and two nonselected control lines was employed. Females only were tested at 8 weeks of age on 2 consecutive days. Testing consisted of placing a C57BL/6 female mouse in the home cage of the isolation-reared wild mouse for 7 min or until an attack occurred. The wild females were rated on a 5-point scale for agonistic behavior, and the sum of the scores over the 2 test days was the criterion for selection. The six lines, each containing ten breeding pairs, were selected for four generations. By the fourth selected generation, the responses of the high and low lines had diverged in the expected directions. One-way analyses of variance indicated reliable differences among high, low, and control lines in the second, third, and fourth generations. It was concluded that female agonistic behavior is influenced by genotype and that the level of this behavior can be manipulated by means of artificial selection.

Age Factors↗
PubMed2006

Dominant-subordinate relationships in hamsters: sex differences in reactions to familiar opponents.

In the majority of mammalian species, males are dominant over and more aggressive than females. In contrast, some reports suggest that female golden hamsters are more aggressive than males but systematic comparisons using the same methods for both sexes are rare. We observed same-sexed pairs of hamsters over repeated trials to assess whether sex differences existed in the level of agonistic behavior and in the development and maintenance of dominant-subordinate relationships with familiar partners. There were no sex differences in measures of agonistic behavior or fear responses (fleeing) during the initial series of three trials on the first day of testing. Following a four-day interval, males that had lost in session 1 showed fearful responses to a familiar dominant male and were not likely to engage in a fight with him. In contrast, females that lost the initial fights were not fearful and fought vigorously with the familiar winner in subsequent encounters. Although the amount of agonistic behavior engaged in by females did decrease over the course of the three sessions, females that lost did not demonstrate an increase in fear, as measured by the latency to flee. Males that lost fights did show increased fear during later trials and sessions. These results suggest that female hamsters are less affected by losing fights than males are and thus that females are less likely than males to develop highly polarized dominant-subordinate relationships. Further work is needed to understand the mechanisms underlying these sex differences.

Aggression↗
PubMed1993

Partial dopamine receptor agonists reverse behavioral, biochemical and neuroendocrine effects of neuroleptics in the rat: potential treatment of extrapyramidal side effects.

The partial DA receptor agonist preclamol, (-)-3-PPP (50-200 mumol/kg, s.c.) partially reversed the catalepsy induced by the dopamine (DA) receptor antagonists haloperidol (5.3 mumol/kg, i.p.) and raclopride (20.1 mumol/kg, i.p.) in rats. Terguride (transdihydrolisuride), a partial DA receptor agonist with an efficacy lower than that of preclamol, blocked haloperidol (10.6 mumol/kg, i.p.) induced catalepsy at 5 mumol/kg, s.c., but not at 20 mumol/kg, s.c. The effects of terguride in this assay are possibly related to the compound's mixed partial DA agonist/5-HT1A receptor agonist properties. The high efficacy agonist, pramipexole (SND 919) also blocked haloperidol induced catalepsy at 50 mumol/kg, s.c. Haloperidol (0.33-1.3 mumol/kg, i.p.) reduced the locomotor activity down to 5% of saline controls and elevated limbic and striatal DOPA accumulation. When combined with haloperidol, preclamol (100-200 mumol/kg, s.c.) antagonized both the strong hypomotility and increase in DOPA accumulation. Finally, the elevation of serum prolactin in rats induced by haloperidol (0.25 mumol/kg, i.p.) was significantly antagonized by co-administration of preclamol (39 mumol/kg, s.c.). These results show that partial DA agonists can reverse both behavioral, biochemical and neuroendocrine effects of neuroleptics. It also suggests the utility of partial DA receptor agonists in combination with classical neuroleptics in order to minimize the appearance of extrapyramidal side-effects and hyperprolactinemia.

Animals↗
PubMed1992

Dissociation between the effects of benzodiazepine receptor agonists on behavioral vigilance and responsitivity.

The effects of benzodiazepine receptor (BZR) full agonists chlordiazepoxide and midazolam, and the partial agonist beta-carboline ZK 91,296 on the rat's performance in a simple reaction time paradigm were examined. This task required the animals to respond to a rarely and unpredictably occurring brief (50 ms) visual stimulus. Non-parametric measures of signal sensitivity and response bias derived from signal-detection theory were used as a basis for the dissociation between the effects of these drugs on attentional abilities and general responsivity. The dose-dependent effects of midazolam (0.1-3.13 mg/kg) on signal sensitivity and general responsivity occurred in parallel. In contrast, the effects of chlordiazepoxide (1.56-12.5 mg/kg) on signal sensitivity were largely independent from effects on response bias. The partial agonist ZK 91,296 (0.39-25 mg/kg) in general had little effect on performance. The effects of the highest doses of chlordiazepoxide and midazolam were reversed by the co-administration of the BZR antagonist Ro15-1788 (15 mg/kg). Additionally, extension of the stimulus presentation time to 500 ms decreased the magnitude of the effect of chlordiazepoxide on signal sensitivity. These results support the hypothesis that BZR agonist-induced disruption of attentional abilities is not necessarily confounded by effects on general responsivity or sedation, and thus may represent a discrete pharmacological property of BZR-agonists.

Animals↗
PubMed1986

Latent aggression-promoting properties of mouse bladder urine activated by heat.

The aggression-promoting property of bladder urine in adult male mice was investigated. Under a newly developed stimulus application procedure (i.e., camel hairbrush applicator). Experiment 1 determined the minimal volume at which bladder and voided urine educed agonistic behavior in agressors. It was found that at least 0.05 ml of bladder urine and 0.03 ml of voided urine, both from intact males, were needed to induce significantly more attacks and uro-anal sniffs than respective urine types from castrated males. Also, bladder urine educed significantly less agonistic behavior than voided urine, both from intact males. Hence, the presence of a weak bladder urine chemosignal was confirmed. From these and previous findings, it was hypothesized that the chemocommunicative property of the weak bladder urine chemosignal could be accentuated by releasing the prochemosignal(s). Using 0.03 ml as the urine volume in Experiment 2, it was shown that heating bladder urine at 37 degrees C educed significantly more agonistic behavior than freezing bladder urine. The heating of bladder urine, however, effected significantly fewer attacks than the freezing of voided urine. It was concluded that bladder urine contains a latent and a free chemosignal, both of which are weak relative to voided urine chemosignal activity.

Aggression↗
PubMed2005

The effects of a selective dopamine D2 receptor agonist on behavioral and pathological outcome in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated squirrel monkeys.

In this study, we investigated antiparkinsonian activity of the novel, highly selective dopamine D(2) receptor agonist sumanirole compared with two clinically effective dopaminergic therapies in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of Parkinson's disease. Squirrel monkeys were rendered parkinsonian by chronic administration of MPTP and subsequently dosed with vehicle, L-DOPA plus carbidopa (L-DOPA), ropinirole, or sumanirole over a duration of 8 weeks. Antiparkinsonian effects measured with a parkinsonian primate rating scale (PPRS) showed that sumanirole elicited improved functional outcome compared with vehicle. The dopamine D2/D3 agonist ropinirole improved behavioral outcome similar to sumanirole, whereas L-DOPA treatment yielded the most significant symptomatic improvement. The relative rank of therapies that elicited normalization of PPRS was L-DOPA > sumanirole; ropinirole did not normalize PPRS in any of the treated monkeys. Dyskinesias were present with L-DOPA treatment but were not observed in sumanirole-, ropinirole-, or placebo-treated primates. Pathologically, all MPTP-treated animals displayed neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta and reactive astrocytosis. Neurons immunoreactive with antibodies to the nuclear transcription factor DeltaFosB were most significantly increased in the striatum of L-DOPA-treated monkeys. These results suggest that sumanirole can exert antiparkinsonian effects similar to L-DOPA without the behavioral and morphological consequences of the latter.

Animals↗
PubMed1997

The effect of prepubertal immunization against gonadotropin-releasing hormone on the development of sexual and social behavior of bulls.

To determine the effect of prepubertal immunization against GnRH on the development of sexual and social behavior of Friesian bulls, 90 calves were randomly assigned to five treatments: 1) I2, immunized against GnRH at 2 and boosted at 2.5, 4, and 7.5 mo of age, n = 2 x 10; 2) I4, immunized against GnRH at 4 and boosted at 4.5 and 7.5 mo of age, n = 2 x 10; 3) I7.5, immunized against GnRH at 7.5 and boosted at 8 mo of age n = 2 x 10; 4) S, steers castrated at 2 mo of age, n = 10; and 5) B, intact bulls, n = 2 x 10. Blood samples were collected initially every 2, then every 3 wk. Plasma was analyzed for anti-GnRH titers and plasma testosterone concentration. Sexual and agonistic behavior, male-male mounting, and damage to paddocks was assessed throughout the experiment. All immunized calves developed antibodies against GnRH (32.3 +/- 2.0% bound at a 1:10 plasma:PBS-BSA dilution, 14 d after first boost). Plasma testosterone concentrations were < 1 ng/mL for all immunized animals until 11 mo of age, when they increased to levels found in intact bulls at 14 mo of age. At slaughter, testes and seminal vesicle weights were 38.3 and 31.6% lighter, respectively, for all immunized treatments compared to B. There were no significant differences between I2, I4, and I7.5 in any of the sexual or agonistic behavior tests. Bulls scored higher than steers in all sexual behavior tests. Immunized bulls scored lower than bulls in sexual behavior tests from 10 to 17 mo of age. The proportion of immunized animals that serviced an estrous cow was lower than the proportion of intact bulls at 10, 12.5, 14, and 17 mo of age. Immunized animals scored lower than bulls in bull challenge tests at 8.5, 11.5, 13, 14.5, and 17 mo of age. Paddock damage by animals on the three immunization treatments was lower than that by bulls from 7 to 14.5 mo of age, as were leg were scores (an indicator of male-male mounting behavior) from 9 to 14 mo of age. There was no difference in sexual behavior between immunized bulls (I2, I4, and I7.5) and bulls while held in lairage pens for 16 h before slaughter, but all treatment groups scored higher than steers. There was a similar trend for agonistic behavior, although I4 bulls were no different from steers. Prepubertal immunization against GnRH at 2, 4, and 7.5 mo of age impaired testes function and affected the development of social and sexual behavior of young bulls.

Aging↗
PubMed1996

MK-801 differentially affects dopamine D1 and D2 receptor agonist-induced behavioral tolerance and desensitization.

In this study we explored the effects of repeated MK-801 (0.10 mg/kg) treatment on rotation in rats with unilateral forebrain dopamine depletions. Daily injections of MK-801 across a 13-day period produced mild ipsilateral rotation which did not change significantly across days compared to daily injections of vehicle. Rats given repeated cotreatment of MK-801 with the selective D1 receptor agonist, A-85653 (0.06 mg/kg), developed response sensitization rather than the behavioral tolerance that was seen in rats given repeated vehicle+A-85653 injections. However, MK-801+A-85653 treated rats did demonstrate behavioral tolerance after an acute vehicle+A-85653 challenge, and the behavioral subsensitivity of rats given repeated vehicle+A-85653 injections reverted to normal in response to an acute MK-801+A-85653 challenge. Thus, MK-801 blocked the expression but not the development of D1-agonist induced behavioral tolerance. MK-801 treatment also enhanced striatal c-fos expression produced by A-85653 but only if MK-801 were given in combination with A-85653 2 h prior to sacrifice; prior daily treatment with MK-801 had no carry-over effect. In contrast to its effects on D1 agonist induced rotation, MK-801 cotreatment inhibited the robust contralateral rotation produced by repeated treatment with the D2/D3 agonist, quinpirole (0.15 mg/kg), and blocked both the development and expression of behavioral supersensitivity compared to rats treated with quinpirole alone. These results demonstrate differential effects of repeated MK-801 treatment on the development and expression of D1 and D2/D3 agonist induced response tolerance and sensitization, respectively.

Animals↗
PubMed1984

Can social and agonistic interactions be used to detect anxiolytic activity of drugs?

Majority of adult male albino random-bred mice housed singly or in small groups show agonistic behavior on interaction with a strange male mouse: some of them are predominantly aggressive ('aggressive' mice) while others show defenses or escapes even though their partners are not aggressive ('timid' mice). The remaining males not exhibiting agonistic behavior ('sociable' mice) show more social investigation then aggressive or timid mice and more locomotion then timid mice. Active defensive-escape behavior ('timidity') and inhibition of social investigation and of locomotion is much stronger in an unfamiliar cage with a strange male than in a home cage or on interaction with a female. Effects of 50 drugs on behavior of aggressive and timid male mice on agonistic interactions with non-aggressive male mice in neutral cages were tested. Most of the drugs possessing anxiolytic activity in man reduced active escapes or defenses at doses lower than those inhibiting attacks or locomotion and increased social investigation while most drugs without anxiolytic activity did not show these effects. Some anxiolytic drugs reduced tail-rattling (an ambivalent activity presumably reflecting both attack and escape tendency) at doses lower than those reducing attacks and increased locomotion. Only some benzodiazepines (nitrazepam, oxazepam and diazepam) produced the whole spectrum of these effects indicating a reduced defensive-escape tendency. The present results suggest that a selective inhibition of defensive-escape tendency on agonistic interactions can be a good predictor of anxiolytic activity of drugs. Profiles of effects of seven benzodiazepines in the present model of agonistic interaction to some extent differed: triazolam, clonazepam and flunitrazepam were more sedating (reduced timidity only at doses inhibiting locomotion) while nitrazepam, oxazepam, diazepam and chlordiazepoxide were less sedating (reduced timidity at non-sedative doses, stimulated social investigation and locomotion). Only drugs stimulating GABA-receptor complex (benzodiazepines, barbiturates and GABAergic drugs) inhibited active escapes and defenses at doses lower than those reducing attacks. This suggests that the GABA-receptor complex is involved in regulation of defensive-escape tendency in intraspecies conflict.

Aggression↗
PubMed1990

Chronic benzodiazepine administration. VI. A partial agonist produces behavioral effects without tolerance or receptor alterations.

Chronic benzodiazepine administration has been reported to lead to behavioral tolerance and, in some cases, downregulation of gamma-aminobutyric acid A (GABAA)-receptor binding and function. So-called "partial agonist" benzodiazepines appear to cause limited benzodiazepine effects and little or no behavioral tolerance. To evaluate behavioral and neurochemical effects of a partial agonist during chronic administration, we treated mice with Ro16-6028, 0.25, 1 and 4 mg/kg/day by implanted osmotic pumps, evaluating open-field activity and binding and function at the GABAA receptor. All three doses of Ro16-6028 caused dose-dependent decreases in vertical movements (rearing), and no tolerance was observed up to 14 days at any dose. In contrast, tolerance occurred to the effects of clonazepam at 7 days. Benzodiazepine receptor occupancy was essentially complete in all brain regions evaluated at doses of 1 and 4 mg/kg/day. Benzodiazepine binding in vivo at 0.25 mg/kg/day was transiently decreased in cortex at 7 days but was unchanged in any other brain region. Benzodiazepine binding in cortex in vitro was unchanged over time at any of the three doses, as were t-butylbicyclophosphorothionate binding and binding at the low- and high-affinity GABA sites measured by [3H]SR-95531. GABAA receptor function as determined by muscimol-stimulated chloride uptake was unchanged over 14 days of administration at Ro16-6028 doses of 0.25 and 4 mg/kg/day. Concentrations of Ro16-6028 were constant during administration at 1 and 4 mg/kg/day. These data indicate that chronic Ro16-6028 causes dose-dependent behavioral effects without the development of tolerance and that, despite substantial or complete benzodiazepine receptor occupancy, few effects occur at the GABAA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗