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The influence of NMDA, a potent agonist of glutamate receptor, on behavioral activity of rats with experimental hyperammonemia evoked by liver failure.

The study was designed to investigate the effects of NMDA receptor agonist on the behavioral activity in rats with experimental hyperammonemia. The experiments were performed on adult male Wistar rats. Experimental hyperammonemia was induced by intraperitoneal injections of tioacetamide (TAA, 200 mg/kg) for three consecutive days. Rats treated with saline (0.9%) served as control. Stimulation of the NMDA glutamatergic receptor was evoked by ip. injection of agonist N-methyl-D-aspartate acid (NMDA) in a dose of 30 mg/kg thirty minutes before experiments. Memory motivated affectively was evaluated in the passive avoidance responses. The speculative influence of the treatment on anxiety and motor activity was tested in elevated plus-maze and in open field respectively. To show change of NMDA receptor function after various doses of agonist, the seizures evoked by N-methyl-D-aspartate acid was carried out. This experiment showed that with rise of dose of NMDA time to appear of convulsions was contracted in rats with hyperammonemia as well as in control rats. Dose of NMDA caused convulsions was three times as less in rats with hyperammonemia than dose in control. Time of duration of convulsions was proportional to applied dose of NMDA and it lengthened with rise of agonist's dose in both groups of studied animals. Furthermore, we observed that NMDA increased motor activity of control rats in open field test, but not in rats with hyperammonemia (treated tioacetamide). Hyperammonemia did not have significant influence on motor activity and on a passive avoidance latency. The NMDA given in control and in hyperammonemia, increased acquisition, consolidation and recall of a passive avoidance responses. Moreover, NMDA had anxiogenic-like profile in elevated plus-maze. In rats with hyperammonemia NMDA had no influence on locomotor activity but it significantly increased memory in a passive avoidance responses. Furthermore, we observed that reactivity of NMDA glutamate receptor in rats with hyperammonemia was higher than in control rats.

Animals↗

Effects of D1 dopamine agonists on schedule-controlled behavior in the squirrel monkey.

Behavioral effects of several dopamine D1 receptor agonists were compared with those of cocaine and (+)-amphetamine in squirrel monkeys trained to press a response key under a fixed-interval schedule of electric shock presentation. Cocaine (0.03 to 0.3mg/kg) and (+)-amphetamine (0.01 to 0.1mg/kg) at low to intermediate doses increased rates of responding under the fixed-interval schedule; at higher doses each of these drugs decreased response rates. In contrast, neither full nor partial D1 receptor agonists produced reliable increases in response rates. Rather, these drugs decreased rates of responding in a dose-related manner. These results with schedule-controlled behavior in primates support earlier findings in rodents that indicate that D1 agonist actions result in effects quite different from the characteristic psychomotor stimulant effects produced by cocaine or (+)-amphetamine; and they further suggest that those characteristic stimulant effects are more probably due to stimulation of other dopamine receptors.

Journal Article↗

Partial limbic kindling--brain, behavior, and the benzodiazepine receptor.

Partial kindling (PK) of the left perforant path (PP) lastingly increased feline defensiveness. Perforant path PK produced long-term potentiation (LTP) in the amygdalo-ventromedial hypothalamic (AM-VMH) pathways in both hemispheres, and in the ventroamygdalofugal (VAF)-VMH efferents of the amygdala of the left hemisphere. Long-term potentiation paralleled behavioral changes. Perforant path PK did not affect recurrent inhibition in area CA3 of the ventral hippocampus. Long-term potentiation of CA3 EPSP and population spikes appeared, but before behavioral changes. Changes in excitability of the periaqueductal grey also accompanied behavioral changes. After kindling, the benzodiazepine receptor antagonist, flumazenil, reduced defensive response to rats in a drug-dependent manner. Flumazenil also reduced LTP in the AM-VMH pathway, but did not affect LTP in the VAF-VMH pathway. Therefore, flumazenil was acting in the amygdala, and not at the VAF-VMH synapse. Kindling caused flumazenil to act like an agonist on behavior, and in the amygdala, and as an agonist or an inverse agonist in area CA3 depending upon the physiological measure taken.

Aggression↗

Dual effect of nucleotides on P2Y receptors.

The interaction of ADP, 2MeSADP, and ADPbetaS with the adenine nucleotide receptor P2Y1 in the hP2Y1-1321N1 cell line and of UDP with a receptor or receptors recognizing pyrimidine nucleotides in NG108-15 cells was studied over a wide range ofligand concentrations. Bell-shaped dose-response curves for stimulation of phosphoinositide hydrolysis were obtained in these cells. This dual behavior of the agonists studied was characterized by two dissociation constants, K(agon) and K(antag), which quantify the agonistic and antagonistic activity of these ligands and can be compared with the conventional EC50 and IC50 values, respectively. The data revealed a common pattern of agonistic and antagonistic behavior of nucleoside diphosphates and their derivatives at these two types of P2Y receptors, pointing to some similar properties of their nucleotide binding sites.

Adenosine Diphosphate↗

Effects of pre-exposure and co-administration of the cannabinoid receptor agonist CP 55,940 on behavioral sensitization to cocaine.

Rats given cocaine (15 mg/kg, i.p.) every second day over a 2-week period displayed a progressively greater locomotor response to the drug over days indicating behavioral sensitization. When the cannabinoid receptor agonist CP 55,940 ((-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hyd roxypropyl)cyclohexanol) (10, 25 or 50 microg/kg) was administered under a similar regime, no such sensitization was observed. Rather, the two highest doses of CP 55,940 (25 and 50 microg/kg) caused locomotor suppression that lasted throughout administration. When rats pre-exposed 10 times to CP 55,940 were challenged with cocaine (15 mg/kg), no exaggerated locomotor response to cocaine was evident relative to non pre-exposed rats. When these rats were subsequently re-tested with CP 55,940, the cannabinoid continued to produce a dose-dependent suppression of locomotor activity. Finally, when CP 55,940 (50 microg/kg) was co-administered with cocaine, it significantly reduced the locomotor hyperactivity produced by the drug but did not block the development of behavioral sensitization. These results show that CP 55,940 does not sensitize locomotor activity with repeated administration in the same way as cocaine, and that pre-exposure or concurrent exposure to CP 55,940 does not enhance sensitivity to the subsequent behavioral effects of cocaine.

Analgesics↗

Gun threats against and self-defense gun use by California adolescents.

OBJECTIVE: To assess hostile gun use against and self-defense gun use by adolescents. DESIGN, SETTING, AND PARTICIPANTS: We use random-digit-dial telephone survey data collected from approximately 5800 California adolescents, aged 12 through 17 years, between November 1, 2000, and October 31, 2001. MAIN OUTCOME MEASURES: The prevalence and correlates of reported hostile gun use against and self-defense gun use by adolescents, as well as qualitative information about these 2 types of gun uses. Correlates include age, sex, ethnicity, smoking, alcoholic binge drinking, threatening others, parents knowing their adolescent's whereabouts in the afternoon after school, attending school, area urbanization and poverty level, and living in a household with a gun. RESULTS: Approximately 4% of the adolescents reported ever having been threatened with a gun; only 0.3% reported using a gun in self-defense. Boys, smokers, adolescents who threatened others, and adolescents whose parents knew little about their whereabouts in the afternoon after school were more likely to report being threatened with a gun. Most episodes of self-defense gun use seem to be hostile interactions between adolescents with weapons. CONCLUSIONS: Far more California adolescents are threatened with a gun than use a gun in self-defense. Self-defense gun use is rare; many of the reported self-defense gun uses seem to be armed confrontations.

Adolescent↗

Partial reversal of behavioral action of the agonist D-Trp-6-LH-RH by naloxone in mice.

The effects of the superactive agonist analog D-Trp-6-LH-RH were investigated in several neuropharmacological tests: inhibition of picrotoxin-induced seizures, open-field behavior, hot-plate and tail-flick tests, assessment of catalepsy and apomorphine-induced cage-climbing. In most tests, D-Trp-6-LH-RH was administered subcutaneously (sc.) at the dose of 100 micrograms/kg. The opiate involvement in the peptide action was checked by using naloxone HCl (NX) in a dose of 1 mg/kg intraperitoneally (ip.), with the exception of the analgesic tests where the dose was 0.5 mg/kg. The analog significantly suppressed the open-field parameters of ambulation, rearing and grooming; except for grooming, these actions were fully antagonized by NX. Similarly, NX pretreatment restored to the control levels the latencies of seizure parameters increased by D-Trp-6-LH-RH. The hot-plate latencies did not change after pretreatment with NX but the opiate antagonist was fully able to antagonize the analgesic effect of the peptide in the tail-flick test. The cataleptogenic effect and the inhibition of apomorphine-induced cage-climbing demonstrated after D-Trp-LH-RH were not antagonized by NX.

Animals↗

Early experience.

Because regulatory mechanisms are not fully developed in neonates, they are particularly susceptible to environmental influences on behavior. Events early in life have the potential for multiplicative effects. Perinatal stress appears to alter the function of the HHA axis in an adaptive manner. Optimal levels of stress might therefore be used in the rearing of domestic animals. Further research, including an assessment of animals' welfare, is needed. The early social environment is of critical importance in behavioral ontogeny. Social conditions other than those with which a species has evolved, such as isolation, rearing without conspecifics, or rearing in single-sex groups, can alter later behavior. Effects on agonistic and sexual behavior, in particular, have been well researched. The types of learning involved in primary socialization are not directly known for most farm species, although other features of socialization are well documented. Nutrition plays an obvious role in physical development. Less obviously, it appears that a low plane of nutrition or protein deficiency can permanently impair learning ability through a decrease in the number of brain neurons.

Animal Nutritional Physiological Phenomena↗

Genetic mechanisms controlling the domestication of a wild house mouse population (Mus musculus L.).

A controlled reenactment of the domestication process provided information on the relative effects of natural selection, inbreeding, and habitat upon an originally wild house mouse population. Effects were assessed by testing offspring that were bred under either laboratory or simulated natural conditions, systematically inbred or outbred, and postnatally fostered in laboratory or simulated natural habitats. Ten generations of domestication failed to reveal any behavioral differences due to either natural selection or habitat on nine different behavioral tests. Inbreeding strongly reduced intermale aggression, partially reduced resistance to recapture by humans, but failed to affect any of the seven other behaviors.

Agonistic Behavior↗

Differentiation between MK-801- and apomorphine-induced stereotyped behaviors in mice.

The ability of phencyclidine (PCP) to model schizophreniform psychosis is believed to be related to its ability to produce both hypoglutamatergia and hyperdopaminergia. As such, identification of PCP-stimulated behaviors may be important for the development of animal models of schizophrenia. In this study, MK-801 [(+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cycloheptane-5,10-imine maleate], a high-affinity PCP analogue, was administered to mice in order to stimulate "PCP behaviors." These PCP behaviors were compared with behaviors stimulated by apomorphine, a dopamine agonist. Stereotyped behavior was assessed by both visual observations and automated measurements. Visual observations showed highly intense gnawing and sniffing in apomorphine-treated mice and the absence of gnawing in MK-801-treated mice. Automated stereotypic measures showed that, compared with vehicle-treated controls, there were frequent dissociations between MK-801 and apomorphine. Conceivably, a compound that attenuates PCP-stimulated behaviors while sparing apomorphine-stimulated behaviors would possess both antipsychotic efficacy and be devoid of undesirable side effects associated with dopamine blockade.

Analysis of Variance↗

Urban youths' perspectives on violence and the necessity of fighting.

OBJECTIVES: To assess youth perceptions of the causes and consequences of violence generally, the causes and consequences of fighting specifically, and to determine how best to approach fighting in the context of violence prevention activities. METHODS: Thirteen structured focus group interviews with youths from three high violence urban settings: a large, urban high school, a training center for disadvantaged youths, and a school for adjudicated youths. Participants were 120 urban, predominately African-American youths and young adults ages 14-22 years (mean: 17.2 years). Seven focus groups were conducted with females, and six with males. RESULTS: Adolescents identified the causes of violence on multiple levels including: individual, family, interpersonal, and community level factors. Most youths (89%) had been in a physical fight. Participants felt that fighting was not "right", but identified situations in which it was necessary. Specifically, fighting was used as a problem solving tool, and could prevent escalation of violence. Youths felt that the adults in their lives, including physicians, were generally ill equipped to give advice about violence, as adults' experiences were so removed from their own. Participants looked to experienced role models to offer problem solving and harm reduction strategies. Youths were open to receiving anticipatory guidance about violence and fighting from primary care physicians they felt comfortable with, and who showed respect for their experiences. CONCLUSIONS: Interventions that include blanket admonitions against fighting should be reassessed in light of youth perceptions that fighting plays a complex role in both inciting and preventing more serious violence.

Adolescent↗

Effects of prenatal ethanol exposure on juvenile play-fighting and postpubertal aggression in rats.

The effects of prenatal ethanol exposure on juvenile play-fighting and postpubertal aggressive behavior in rats were longitudinally assessed in the context of more conventionally applied physical and behavioral measures. Pregnant animals were treated with either 2 gm/kg/day ethanol or isocaloric sucrose over gestation Days 6-19. Reproduction and somatic variables included maternal weight over gestation, offspring weight over Days 1-90, and age at eye opening and incisor eruption. Behavioral variables consisted of negative geotaxis, olfactory discrimination, activity, juvenile play-fighting, and postpubertal aggression. Ethanol offspring had lower birth weights, but there was no significant prenatal treatment effect on subsequent offspring weights or on any other reproductive or somatic variable. Both male and female ethanol-exposed offspring exhibited more play-fighting responses when paired with same-sex controls. Postpubertal aggression levels were assessed in males only. Ethanol-exposed offspring were more aggressive than controls and there was a significant positive correlation between play-fighting and postpubertal aggression ranks. No other behavioral measures discriminated between prenatal treatment groups and none were significantly correlated with either play-fighting or postpubertal aggression rank. The results are consistent with the position that juvenile play-fighting and postpubertal aggression are subserved by common substrates. They also are consistent with predictions derived from the hypothesis concerning a response-inhibition deficit as an effect of prenatal ethanol exposure on behavior.

Aggression↗

Applications of behavior to poultry management.

The application of poultry behavior to management is discussed with examples of behavior-management interactions relating to commercial poultry husbandry practices. Behaviors that are important for the adaptation of poultry to husbandry include: social behavior, aggression, sexual behavior, feeding, broodiness, cannibalism, nest site selection, and comfort behaviors.

Agonistic Behavior↗

Activation of metabotropic glutamate 2/3 receptors reverses the effects of NMDA receptor hypofunction on prefrontal cortex unit activity in awake rats.

Systemic exposure to N-methyl-d-aspartate (NMDA) receptor antagonists can lead to psychosis and prefrontal cortex (PFC)-dependent behavioral impairments. Agonists of metabotropic glutamate 2/3 (mGlu2/3) receptors ameliorate the adverse behavioral effects of NMDA antagonists in humans and laboratory animals, and are being considered as a novel treatment for some symptoms of schizophrenia. Despite the compelling behavioral data, the cellular mechanisms by which potentiation of mGlu2/3 receptor function attenuates the effects of NMDA receptor hypofunction remain unclear. In freely moving rats, we recorded the response of medial PFC (prelimbic) single units to treatment with the NMDA antagonist MK801 and assessed the dose-dependent effects of pre- or posttreatment with the mGlu2/3 receptor agonist LY354740 on this response. NMDA receptor antagonist-induced behavioral stereotypy was measured during recording because it may relate to the psychotomimetic properties of this treatment and is dependent on the functional integrity of the PFC. In most PFC neurons, systemic administration of MK801 increased the spontaneous firing rate, decreased the variability of spike trains, and disrupted patterns of spontaneous bursts. Given alone, LY354740 (1, 3, and 10 mg/kg) decreased spontaneous activity of PFC neurons at the highest dose. Pre- or posttreatment with LY354740 blocked MK801-induced changes on firing rate, burst activity, and variability of spike activity. These physiological changes coincided with a reduction in MK801-induced behavioral stereotypy by LY354740. These data indicate that activation of mGlu2/3 receptors reduces the disruptive effects of NMDA receptor hypofunction on the spontaneous spike activity and bursting of PFC neurons. This mechanism may provide a physiological basis for reversal of NMDA antagonist-induced behaviors by mGlu2/3 agonists.

Action Potentials↗

Influence of NMDA, a potent agonist of glutamate receptors, on behavioral activity in 4-week streptozotocin-induced diabetic rats.

The study was designed to investigate the effects of NMDA receptor agonist on the behavioral activity in rats with experimental diabetes mellitus (DM). Experimental diabetes was induced by a single intravenous injection of streptozotocin at a dose of 65 mg/kg dissolved in saline. Rats treated with saline (0.9%) served as control. Stimulation of the NMDA glutamatergic receptor was evoked by ip injection of an agonist N-methyl-D-aspartate acid (NMDA), at a dose of 15 mg/kg 30 min before the experiments. Memory motivated affectively was evaluated in the passive avoidance responses. Possible influence of the treatment on locomotor and exploratory activity was tested in open field test. Moreover, the working memory was evaluated in the T-maze test. We observed that NMDA given alone did not have significant influence on motor activity in control rats except for the number of bar approaches, while in rats with DM NMDA significantly increased motor activity in the open field test. In rats with experimental diabetes, NMDA increased acquisition, but it did not have any significant influence on consolidation and recall of a passive avoidance responses. NMDA at the tested dose had no influence on a passive avoidance latency in control rats. In the T-maze test, NMDA increased working memory but only in diabetic rats.

Animals↗

ACTH-induced behaviors and their modulation by serotonergic agonists differ in neonatal and weanling rat pups.

Four-day-old (P4) and 21-22-day-old (P21-22) rat pups received an intracisternal injection of either ACTH1-16NH2 or saline followed by a subcutaneous (SC) injection of saline, the serotonergic (5HT)1A agonists 8-OH-DPAT or ipsapirone, the 5HT1B agonist TFMPP or the 5HT2 agonist DOI. The ontogeny of ACTH-induced behaviors including grooming, yawn and stretch as well as various serotonin-related behaviors were recorded via time-sampling at 20 s intervals for a test duration of 50 min. ACTH induced slight but significant increases in grooming at P4, along with a significant increase in yawning. At this age the 5HT1B agonist TFMPP induced substantial increases in grooming, with no effect of the other agonists on this behavior. All of the serotonergic agonists, however, decreased ACTH-induced yawning at P4. At P21-22 ACTH induced more robust grooming than that observed at P4, although different in nature from adult-typical ACTH-induced grooming. This ACTH-induced grooming at P21-22 was attenuated by all of the serotonergic agonists. ACTH-induced yawning at P21-22 was not affected by the serotonergic agonists while ACTH-induced stretching was increased by the 5HT1B agonist TFMPP at this age. These data provide additional evidence of differential mediation of various ACTH-induced behaviors, and support other reports of ontogenetic alterations in the response to serotonergic manipulations during the neonatal to weanling age period.

Adrenocorticotropic Hormone↗

Behavioral demonstration of a reciprocal interaction between dopamine receptor subtypes in the mouse striatum: possible involvement of the striato-nigral pathway.

It is well known that stimulation of the D-2 dopamine receptor in vitro inhibits the increased efflux of cyclic adenosine monophosphate caused by D-1 receptor agonists. Furthermore, behavioral data suggest that the striato-nigral pathway is more involved with the dopamine agonist-induced expression of oral behaviors, which are, in turn, mediated by stimulation of the D-1 receptor. We examined an in vivo model to determine whether this D-1/D-2 reciprocal interaction is detectable at a behavioral level. First, mice were pretreated with wide range of doses of the D-2 antagonist, spiperone, and then injected with a behaviorally active dose of apomorphine (a nonspecific direct dopamine agonist) and were observed for incidence of oral behavior and rated for stereotypic behavior. A biphasic effect of spiperone pretreatment was observed, at some low doses both stereotypy and oral behavior were enhanced, while at high doses, both agonist-induced behaviors were progressively inhibited. To test the specificity of this effect for the striato-nigral pathway, mice were administered discrete electrolytic lesions in the ventral portion of the internal capsule in one hemisphere. The animals that responded to apomorphine by rotating ipsilaterally to the lesion were used in two, five-point apomorphine dose-response curves, one with, and one without, pretreatment with the dose of spiperone which most enhanced stereotypic behavior and incidence of oral behavior. The spiperone pretreatment caused a clear increase in the maximum rotational response to apomorphine without affecting the ED50. These data suggest that behavior associated with the striato-nigral efferent from striatum is marked by the opposition of D-1 and D-2 receptors.

Animals↗