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PubMed1995

Sexual attraction and copulation in male rats: effects of the dopamine agonist SND 919.

Behavioral differences towards receptive females, involving latency to the first contact, amicable behavior, genital exploration, and copulatory pattern, were seen in sexually active (A), sluggish (S), and inactive (I) male rats classified on the basis of 11 consecutive mating tests. The D2 dopamine agonist SND 919 (1 mg/kg) was intraperitoneally administered to the three groups 25 min before a 12th test; the drug stimulated the copulatory behavior of A and S but not of I rats in which it diminished genital exploration and amicable behavior. In a 13th test, conducted 1 week later, 31% of I initiated mating, 16% of them reaching ejaculation. The stimulant effect of SND 919 on copulation in A rats was confirmed in further experiments where it was injected at 0.1 mg/kg, a dose selective for the D2 autoreceptors.

Animals↗
PubMed1986

Seasonality of adult male Japanese macaques (Macaca fuscata): androgens and behavior in a confined troop.

Seasonal variations in levels of serum testosterone, dihydrotestosterone (DHT), reproductive behavior, and social behavior were investigated in 12 adult males (5 to 20+ years of age) of the Oregon troop of Japanese macaques (Macaca fuscata). Blood samples were collected at 2- to 4-month intervals, and behaviors were monitored twice weekly over a 15-month period. Significant seasonal variations in levels of testosterone and DHT, and in frequencies of mount series, ejaculations, number of female partners, displays, courtship, and aggression were observed. Seasonal variations in reproductive and social behaviors did not correlate with seasonal variations in androgen levels because seasonal increases in these behaviors followed seasonal increases in the androgens with a 1- to 2-month delay. However, significant correlations between increased androgen levels and the onset of mating activity occur when mean monthly frequencies of mount series are shifted 1 to 2 months earlier to coincide with the rise in serum androgen levels. The frequency of adult male play and male-male mounting increased significantly when androgen levels were low. We suggest that photoperiod changes may function as a proximate cue in male Japanese macaques which induces a state of biological readiness for mating, and the behavioral consequences (i.e., mating) are then dependent upon the presence of receptive females.

Agonistic Behavior↗
PubMed1982

Mouse killing in rats: a comparison of spontaneous killers and rats with lesions of the medial hypothalamus or the medial accumbens nucleus.

Mouse killing was observed and videotaped at forty-eight hr following surgery in rats with lesions of the medial hypothalamus or the medial accumbens. The initial attacks and killing bites of the lesioned rats were directed at the anterior dorsal surface, predominantly to the regions of the neck, shoulders, and thorax and did not differ from those of spontaneous mouse killing rats. The latency to attack was significantly shorter for the lesioned animals but the time required to kill following the attack tended to be longer. Lesioned animals spent significantly more time biting the prey following the kill and left significantly more bite marks on the prey than did the spontaneous killers. When the dead prey was moved about the cage following the kill, the lesioned animals showed a significantly greater tendency to attack it than did the spontaneous killers. Following the test of mouse killing, each rat was successively exposed to a freshly killed mouse, a cotton wad, and a wood block. The lesioned animals attacked the dead mouse and the cotton wad as though they were live mice whereas the spontaneous killers did not. These results suggest that while the killing is similar for lesioned and spontaneous killers, the lesioned animals show a heightened response to the killing experience. This is manifested in an exaggeration of attack behaviors toward prey and prey-like stimulus objects following an initial killing experience.

Aggression↗
PubMed1986

Ventromedial tegmental lesions abolish offense without disturbing predation or defense.

Offense, defense, and predation, three kinds of aggressive behavior, are differentially affected by lesions of the ventromedial tegmentum of the brainstem of the rat. The lesions abolish offense while leaving defense and predation undisturbed. The offense behavior against another strange male, including bite-and-kick attack, offensive sideways posture, and offensive upright posture, was totally abolished, while the rats showed intact motor patterns of defensive upright posture, chasing, and killing bite in the tests for defense and predation. It is argued that these results support a motivational systems analysis of mammalian aggressive behavior. According to such an analysis, offense, defense, and predation are controlled by discrete motivational mechanisms located in different brainstem regions.

Aggression↗
PubMed2006

The influence of the time course of inflammation and spinalization on the antinociceptive activity of the alpha2-adrenoceptor agonist medetomidine.

The purpose of the present study was to investigate the influence of the time course of inflammation and the implication of spinal and supraspinal sites on the antihyperalgesic effects of the alpha(2)-adrenoceptor agonist medetomidine. Behavioral experiments showed a more intense antihyperalgesia in the phase of maintenance of inflammation than in the early or resolution stages. Maximum effect, without sedation, was observed with a dose of 40 microg/kg (66+/-12% and 76+/-15% reduction of mechanical and thermal hyperalgesia). No change was observed in the paw swelling, indicating that its effects were not secondary to a reduction of inflammation. In electrophysiological experiments, the effect was more pronounced in animals with an intact spinal cord than in spinalized animals (max. effects of 2+/-0.7% vs. 48+/-11% of control, noxious mechanical stimulation). We conclude that the antihyperalgesic effect of medetomidine depends on the time course of inflammation and that it is mainly located supraspinally.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2004

Ethologically based resolution of D2-like dopamine receptor agonist-versus antagonist-induced behavioral topography in dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein of 32 kDa "knockout" mutants congenic on the C57BL/6 genetic background.

Given the critical role of dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein of 32 kDa (DARPP-32) in the regulation of dopaminergic function, DARPP-32-null mutant mice congenic on the inbred C57BL/6 strain for 10 generations were examined phenotypically for their ethogram of responsivity to the selective D2-like receptor agonist RU 24213 (N-n-propyl-N-phenylethyl-p-3-hydroxyphenylethylamine) and the selective D2-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide), using procedures that resolve all topographies of behavior in the natural repertoire. After vehicle challenge, levels of sniffing and rearing seated were reduced in DARPP-32 mutants; the injection procedure seems to constitute a "stressor" that reveals phenotypic effects of DARPP-32 deletion not apparent under natural conditions. Topographical effects of 0.3 to 10.0 mg/kg RU 24213, primarily induction of sniffing and ponderous locomotion with accompanying reductions in rearing, grooming, sifting and chewing, were not altered to any material extent in DARPP-32-null mice. However, topographical effects of 0.005 to 0.625 mg/kg YM 09151-2, namely, reduction in sniffing, locomotion, rearing, grooming, and chewing but not sifting, were essentially absent in DARPP-32 mutants. Thus, the D2-like receptor agonist-mediated ethogram was essentially conserved, whereas major elements of the corresponding D2-like receptor antagonist-mediated ethogram were essentially absent in DARPP-32-null mice. This suggests some relationship between 1) extent of tonic dopaminergic activation of DARPP-32 mechanisms and 2) compensatory mechanisms consequent to the developmental absence of DARPP-32, which may emerge to act differentially on individual elements of the DARPP-32 system. Critically, the present data indicate that phenotypic effects of a given gene deletion using an agonist acting on the system disrupted cannot be generalized to a corresponding antagonist, and vice versa.

Animals↗
PubMed1995

The cannabinoid agonists WIN 55,212-2 and CP 55,940 attenuate rotational behavior induced by a dopamine D1 but not a D2 agonist in rats with unilateral lesions of the nigrostriatal pathway.

The effect of cannabinoid receptor stimulation on rotational behavior induced by a dopamine D1 and a D2 agonist was studied in rats with unilateral 6-hydroxydopamine-induced lesions of the dopaminergic nigrostriatal pathway. The cannabinoid agonists WIN 55,212-2 (2.5 mg/kg) and CP 55,940 (0.1 mg/kg) both markedly attenuated contralateral rotation induced by the D1 agonist SKF 38393 (1.5 mg/kg). In contrast, WIN 55,212-2 and CP 55,940 did not alter rotation elicited by the D2 agonist quinpirole (0.1 mg/kg). Doses of WIN 55,212-2 and CP 55,940 that attenuated D1-mediated rotation did not produce catalepsy in intact rats or in rats with 6-hydroxydopamine-induced lesions, indicating that the reduction in rotation produced by the cannabinoids was not due to a generalized motor impairment. In addition, the effective dose of WIN 55,212-2, but not CP 55,940, produced only a slight increase in ipsilateral rotation when administered alone, making it improbable that this ipsilateral tendency accounts for the reduction in D1-mediated contralateral rotation. These results suggest a preferential interaction between cannabinoid receptor stimulation and dopamine D1 receptor-mediated behavior.

Animals↗
PubMed1993

Genetic mediation of infanticide and parental behavior in male and female domestic and wild stock house mice.

Infanticide is a reproductive strategy found in many mammals, especially rodents. The proportion of male and female house mice (Mus domesticus) that are either infanticidal or noninfanticidal is strain specific and varies widely from stock to stock. Male house mice also show strain-specific variation in the behavioral mechanisms that inhibit infanticidal individuals from killing their own offspring. The adult offspring generated from reciprocally crossed CF-1 and Wild stock house mice were tested for their behavior toward newborn pups. In male CF-1 x Wild hybrids, the proportion of infanticidal and noninfanticidal males matched with their maternal phenotype, whereas female CF-1 x Wild hybrids exhibited a proportion of behaviors typical of the CF-1 phenotype, regardless of their mother's genotype. Our results suggest three conclusions: first, that infanticide is a highly labile and heritable behavior in both sexes; second, that there is a sex difference in the genetic substrate that regulates the inheritance of infanticidal behavior; and third, that selection pressures in male mice may operate independently on the mechanisms that promote spontaneous infanticidal behavior versus the mechanisms that inhibit infanticide.

Agonistic Behavior↗
PubMed2001

Stress-induced changes in brain serotonergic activity, plasma cortisol and aggressive behavior in Arctic charr (Salvelinus alpinus) is counteracted by L-DOPA.

Arctic charr (Salvelinus alpinus) were tested for aggressive behavior using intruder tests, before and after 2 days of dyadic social interaction. Following social interaction, half of the dominant and half of the subordinate fish were given L-DOPA (10 mg/kg, orally), whereas the remaining dominant and subordinate fish were given vehicle. One hour following drug treatment, the fish were tested for aggressive behavior again in a third and final intruder test, after which blood plasma and brain tissue were sampled for analysis of plasma cortisol concentrations and brain levels of monoamines and monoamine metabolites. Subordinate fish showed a reduction in the number of attacks launched against the intruder, as well as an increase in attack latency, as compared to prior to dyadic social interactions. Social subordination also resulted in an elevation of brain serotonergic activity. Fish receiving L-DOPA prior to the final intruder test showed shorter attack latency than vehicle controls. Drug treatment was a stressful experience and vehicle controls showed elevated plasma cortisol levels and longer attack latency as compared to before treatment. L-DOPA-treated fish showed lower plasma levels of cortisol and lower serotonergic activity in certain brain areas than vehicle controls. These results suggest that L-DOPA counteracts the stress-induced inhibition of aggressive behavior, and at the same time inhibits stress-induced effects on brain serotonergic activity and plasma cortisol concentrations.

Aggression↗
PubMed1983

Differential effects of dopaminergic agonists on food-reinforced operant behavior in the long-tailed macaque (Macaca fascicularis).

Dopaminergic involvement in the regulation of operant behavior was examined by monitoring responding after administration of different dopaminergic agonists. A chain schedule of reinforcement was used to classify the effects of these agonists in long-tailed macaques (Macaca fascicularis). The schedule included the following: (1) a 30-s time-out period; (2) a clock-cued 30-s period of differential reinforcement of zero-response rate; (3) a time-in period whose duration depended on response latency; (4) a 2-s reinforcement period in which applesauce was delivered. This cycling schedule maintained a low operant rate and was sensitive to both inhibition (decreases) and excitation (increases) of responding. IV injection of the dopaminergic agonists resulted in the following two basic effects: (1) d-amphetamine and amfonelic acid disrupted performance by response inhibition, which was shown not to be attributable to anorexia; (2) apomorphine and bromocriptine disrupted performance by response excitation. Both effects were reduced by pretreatment with trifluperidol, a dopaminergic antagonist. The results, indicating that dopaminergic systems mediate disruption of food-reinforced operant behavior by altering the frequency of responding, are interpreted in terms of the known neuropharmacological actions of the agonists.

Animals↗
PubMed1996

Role of receptor phosphorylation in desensitization and internalization of the secretin receptor.

The secretin receptor is prototypic of a recently described family of G protein-coupled receptors. We recently demonstrated its phosphorylation in response to agonist stimulation and elimination of this covalent modification by C-terminal truncation (F. Ozcelebi et al. (1995) Mol. Pharmacol. 48, 818-824). Here, we explore the functional impact of receptor phosphorylation and structural determinants for desensitization by comparing receptor behavior after agonist exposure in cell lines expressing wild-type and truncated receptor. To characterize receptor internalization, a novel fluorescent full agonist, [rat secretin-27]-Gly-rhodamine, was developed, which bound specifically and with high affinity. Both receptor constructs bound secretin normally, leading to normal G protein coupling and cAMP accumulation and prompt receptor internalization. Exposure to 10 nM secretin for 5 min or 12 h prior to washing and restimulation with a full range of concentrations demonstrated absent cAMP responses in wild-type receptor-bearing cells and responses 25 to 30% of control and shifted 1 order of magnitude to the right in the truncated receptor-bearing cells. Thus, the major mechanism of desensitization was phosphorylation-independent receptor internalization. Phosphorylation was associated with a distinct process that likely represents interference with G protein coupling, manifest as a reduced rate of cAMP stimulation. Thus, dual distinct mechanisms of desensitization exist in the secretin receptor family that should help protect receptor-bearing cells from overstimulation.

Animals↗
PubMedDate not supplied

Rural elementary students', parents', and teachers' perceptions of bullying.

OBJECTIVE: To examine the prevalence and correlates of bullying in 7 rural elementary schools from students', parents', and teachers' perspectives. METHOD: Surveys were completed by 739 fourth, fifth, and sixth grade students, 367 parents, and 37 teachers. RESULTS: Students tended to report higher prevalence of bullying than did parents or teachers, and their reports were associated with aggression, attitudes toward violence, and perceptions of school safety. CONCLUSION: Bullying behavior is prevalent in rural elementary schools and is indicative of aggression and proviolence attitudes. Parents and teachers need to pay closer attention to bullying behavior among schoolchildren and to impart their knowledge to children in a comprehensive, coordinated manner.

Agonistic Behavior↗
PubMed1988

[Species differences in the behavioral effects of cerulein--an agonist of the receptors of the octapeptide cholecystokinin--in white mice and rats].

It has been shown in the behavioural experiments that combined pretreatment with haloperidol (0.25 mg/kg) and caerulein (40 micrograms/kg), and to a lesser extent pretreatment with caerulein alone caused long-term reversal of amphetamine (2 mg/kg) induced hyperexcitability in rats. Administration of proglumide (50 mg/kg), an antagonist of CCK-8 receptors, did not reverse long-term antiamphetamine effect of caerulein. In mice pretreatment with caerulein (50 and 100 micrograms/kg) alone or in combination with haloperidol (0.25 mg/kg) caused hypersensitivity to the behavioural effect of amphetamine (3 mg/kg). Intraventricular (I ng), but not systemic (100-500 micrograms/kg) administration of caerulein selectively antagonized seizures in mice induced by intraventricular administration of quinolinic acid (5 micrograms) and N-methyl-D-aspartate (0.2 microgram). Pretreatment with proglumide (50 mg/kg) reversed the anticonvulsive effect of caerulein in mice. In rats, caerulein failed to affect the seizures caused by intraventricular administration of quinolinic acid. The results of the present study demonstrate the existence of obvious interspecies differences in the behavioural effects of caerulein, the agonist of CCK-8 receptors, in mice and rats.

Amphetamine↗
PubMed1986

The pathophysiological functions mediated by D1 dopamine receptors.

The administration of the D1 DA receptor antagonist SCH 23390 produces catalepsy in rat, and this behavior can be abolished by pretreatment with selective D2 DA receptor agonists. The administration of mixed D1/D2 DA agonists, but not of selective D2 DA agonists, produces SMB behavior in monkeys with surgical unilateral VMT lesions of the brain stem. The DA agonist-induced SMB behavior is abolished by pretreatment of the monkeys with either the D1 DA antagonist SCH 23390 or with the mixed D1/D2 antagonist fluphenazine, but not with the selective D2 antagonist (+/-) sulpiride. A hypothetical relationship between abnormal guanine nucleotide metabolism in Lesch-Nyhan syndrome and the development of DA receptor supersensitivity is presented. The possible role of abnormal guanine nucleotide metabolism in some mental disorders associated with DA dysfunctions is discussed.

Animals↗
PubMed1990

Behavioral and neuroendocrine response to psychosocial stress in male rats: the effects of the 5-HT 1A agonist ipsapirone.

The effect of the 5-HT 1A agonist ipsapirone on the behavior, plasma catecholamine, and corticosterone levels was studied in male Wistar rats during the psychosocial stress of confrontation with a confined dominant opponent 24 hr after defeat. The effect of the drug was also studied during a predefeat confrontation with the confined (would-be dominant) rat. Blood samples were withdrawn via a permanent heart catheter. The drug (5 mg/kg, ip) or vehicle was given 30 min before transportation to the experimental room. Ipsapirone had no major effects on the plasma hormone concentrations and had no influence upon the behavioral response to the confined rat. At the postdefeat test ipsapirone led to a significant increase of immobility, whereas both rearing and time spent sniffing the cage were diminished. Postdefeat psychosocial stress resulted in an increase of the hormone, particularly catecholamine levels. These responses were further elevated by the drug. The presence of high corticosterone levels in the home cage after postdefeat ipsapirone treatment leads to the hypothesis that postsynaptic 5-HT 1A receptor hypersensitivity develops after the social stress of defeat.

Agonistic Behavior↗
PubMed1988

Facilitatory effects of caerulein on hypothalamic defensive attack in cats.

Effects of intraventricularly microinjected caerulein (0.1, 1.0 and 10.0 micrograms) on the thresholds for hypothalamically elicited defensive attack and influences of haloperidol (0.5 mg/kg, i.p.) on the effects were studied in chronic cats. Directed attack and hissing were selected for threshold determination, and thresholds for these responses were measured under two situations: one with provocations by a human, and the other without such provocation. Results were as follows. (1) Caerulein lowered all thresholds in generally equal decrements and in a dose-related manner, accompanied by a general behavioral arousal. (2) Prior injection of haloperidol prevented the effects of caerulein, suggesting an antagonism-like interaction between haloperidol and caerulein. (3) Observed facilitatory effects of caerulein on the hypothalamic defensive attack were very similar to those observed with dopamine (DA) agonists such as methamphetamine and apomorphine and opposite to those with DA antagonists such as haloperidol and chlorpromazine. These findings suggest that caerulein exerts its facilitatory effects on the excitability of the ventromedial hypothalamic nucleus through its synergistic interaction with DA.

Aggression↗
PubMed1985

Effects of opiate antagonists and putative kappa agonists on unpunished and punished operant behavior in the rat.

The effects of naloxone and diprenorphine, opiate antagonists with different receptor-binding properties, and the putative kappa-receptor agonists, ketocyclazocine and ethylketocyclazocine (EKC), were studied on food-reinforced responding in rats. Behavior was maintained under a multiple-component 1-min variable-interval schedule in which 12-min periods of unpunished responding alternated with 4-min periods in which each response was punished by a brief electric footshock. Daily sessions were 1 h. Naloxone (0.01-10 mg/kg) decreased unpunished responding only slightly; punished responding was decreased significantly to 66% of control by 10 mg/kg. Diprenorphine (0.01-10 mg/kg) did not affect unpunished responding and increased punished responding dose-dependently to as much as 190% of control. EKC (0.01-1.0 mg/kg) decreased unpunished and punished responding dose-dependently and comparably, whereas ketocyclazocine (0.01-1.0 mg/kg) decreased unpunished responding but did not significantly affect punished responding. Diprenorphine was more potent than naloxone in blocking the decreases in responding produced by the kappa agonists. Differences in the behavioral effects of naloxone and diprenorphine appear to reflect the different receptor-binding properties of the two opiate antagonists.

Animals↗
PubMed1996

Behavioral and biochemical characterization of benzodiazepine receptor partial agonists in pigeons.

The ability of benzodiazepine receptor partial agonists to exhibit full efficacy in preclinical anxiolytic tests, in conjunction with initial clinical results, has suggested the possibility of a reduced clinical side-effect profile compared to benzodiazepine receptor full agonists like diazepam. Because punished behavior of pigeons has been useful in detecting effects of novel anxiolytic drugs, effects of imidazobenzodiazepine and beta-carboline benzodiazepine receptor partial agonists and some related compounds were evaluated in this species. The abilities of these compounds to substitute for the discriminative stimulus effects of the full agonists midazolam also was determined. Intrinsic efficacy was assessed by the degree to which gamma-aminobutyric acid increased ligand potency to displace [(3)H]Ro15-1788 (flumazinil) from membranes of pigeon cerebrum, and ranged from full agonist-like efficacy (Ro 19-5470; 7-(3-cyclopropyl-1,2,4-oxodiazol-5-yl)-5,6-dihydro-5-methyl-4H- imidazo[1,5a]-thieno[3,2-f]diazin-4-one) to minimal gamma-aminobutyric acid potentiations close to that of the antagonist flumazenil (abecarnil and Ro 41-7812; 7-chloro-4,5-dihydro-3-(3-hydroxy-1-propynyl)-5-methyl-6H-imidazo[1,5-a] -[1,4 ]benzodiazepine-6-one). Punished responding was increased markedly by midazolam and by all partial agonists, except Ro 41-7812 and Ro 42-8773 (7-chloro-3-[3-(cyclopropylmethoxy)-1-propynyl]-4,5-dihyro-5 -methyl-6H-imidaz o[1,5-a][1,4]benzodiazepine-6-one), at doses that did not affect nonpunished responding. In contrast to the full substitution generally observed in mammals, all of the partial agonists produced incomplete substitution (40-70%) in the midazolam drug discrimination procedure in pigeons. A positive relationship was observed between the degree of substitution and intrinsic efficacy. The benzodiazepine antagonists, flumazenil and ZK 93,426 (ethyl-5-isopropoxy-4-methoxymethyl-beta-carboline-3-carboxylate), neither increased punished responding nor substituted for midazolam. The results of the present study suggest that benzodiazepine receptor partial agonists and related compounds may provide full anxiolytic activity at doses that do not fully reproduce the subjective effect profile of full agonists.

Animals↗