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D2 dopamine receptor antisense oligodeoxynucleotide inhibits the synthesis of a functional pool of D2 dopamine receptors.

In vivo administration of an antisense oligonucleotide targeted toward the D2 dopamine (DA) receptor mRNA (D2 AS) markedly inhibited D2 receptor-mediated behaviors but produced only a relatively small reduction in the levels of D2 DA receptors in mouse striatum. This apparent dissociation between DA receptor-mediated behaviors and the levels of D2 DA receptors was addressed by inhibiting the total number of D2 DA receptors by intraperitoneal administration of the selective, irreversibly acting D2 DA receptor antagonist fluphenazine-N-mustard (FNM) and then determining the effects of D2 AS, administered intracerebroventricularly, on the rate of synthesis of D2 DA receptors and on the recovery of D2 receptor-mediated behaviors. FNM inactivated approximately 90% of D2 DA receptors within 4 hr of treatment, after which the receptors returned to normal levels by approximately 8 days. D2 AS treatment significantly inhibited the rate of recovery of D2 DA receptors in striatum of FNM-treated mice. FNM treatment also produced a number of behavioral alterations, including catalepsy, and the inhibition of stereotypic behavior induced by the D2/D3 DA receptor agonist quinpirole. Both of these behaviors returned to normal within 8 days after FNM treatment. D2 AS treatment delayed the restoration of these FNM-induced behaviors. Thus, it reduced the rate of disappearance of the cataleptic behavior induced by FNM and significantly delayed the restoration of the stereotypic behavior induced by quinpirole. The changes induced by D2 AS on D2 receptor-mediated behaviors were reversed on cessation of D2 AS treatment. A random oligomer given in the same amount and for the same length of time as that of the D2 AS had no significant effects on either D2 DA receptor synthesis or DA receptor-mediated behaviors. These studies demonstrate that in vivo administration of D2 AS decreased the rate of recovery of D2 DA receptors and inhibited the recovery of D2 DA receptor-mediated behaviors after irreversible receptor inactivation and suggest that D2 AS treatment inhibits the synthesis of a functional pool of D2 DA receptors.

Animals↗

Perceived consensus influences intergroup behavior and stereotype accessibility.

Past research has demonstrated the powerful influence other people have on the thoughts and behaviors of individuals. However, the study of intergroup attitudes has focused primarily on the influence of direct exposure to out-group members as determinants of stereotypes and prejudice. Two experiments tested the hypothesis that learning that others share one's intergroup beliefs influences intergroup attitudes and behavior as well as stereotype representation. Experiment 1 demonstrated that learning that one's beliefs are shared or not shared with others influences attitudes, behavior, and the strength of the attitude-behavior relationship. Experiment 2 demonstrated a potential mechanism for such effects by showing that learning about whether others share one's stereotypes influences the accessibility of those stereotypes and related stereotypes.

Adult↗

Atropine stereotypy as a behavioral trap: a movement subsystem and electroencephalographic analysis.

An analysis was made of the movement subsystems involved in the stereotyped behaviors and electroencephalographic (EEG) activity that appear in rats given the anticholinergic drug atropine sulfate (50-75 mg/kg). One form of stereotypy occurred when the drugged faced the closed end of an alleyway. Instead of scanning briefly and then turning around to face the open end, as undrugged rats do, they typically "trapped", i.e., they continued to engage in rapid, repetitive scanning by the snout up and down or side to side along the surfaces of the closed end for long periods of time. Atropine appears to produce an exaggerated snout thigmotaxis. Accordingly, the behavioral pattern can be manipulated simply by changing the configuration of the environment, which alters sensory input to the snout. Therefore, such stereotyped behavior is not a motor automatism but rather a circular chain of reflexive reactions to surfaces which trap the animal. During rapid shifts in direction of movement in undrugged rats, there were often extremely brief periods of hippocampal theta that could be blocked by atropine. The presence of theta during such shifts might be important for normal behavioral sequencing. This could partially account for the fact that atropine-treated rats failed to change from their initial reactions in the alleyway to more adaptive behaviors. When a low roof was placed over the alleway, head scanning was greatly limited, and immobility in a lying posture rapidly became the more frequent behavior. This immobility was accompanied by a sleeplike (synchronized) neocortical EEG pattern rather than the activated (desynchronized) neocortical pattern that occurs during repetitive thigmotactic scanning. It is hypothesized that scanning stereotypy and activated EEG are maintained through movement-concurrent positive feedback.

Animals↗

A comparative study of different amphetamines on copulatory behavior and stereotype activity in the female rat.

The influence of D- and L-amphetamine, fenfluramine, and p-chloroamphetamine on female copulatory behavior (lordosis response) and the induction of stereotype activity was compared. Lordosis response in the female rat has been shown to be inhibited by increased central nervous serotonergic (5-HT) as well as dopaminergic (DA) activity. A dose-dependent inhibitory effect on the estrogen- + progesterone-induced lordosis response in ovariectomized rats was demonstrated after treatment with the four amphetamines. In contrast, only D- and L-amphetamine induced a stereotype activity, which is considered to be mediated by DA mechanisms. A decrease in DA receptor activity, achieved by pimozide pretreatment, abolished the effect of D-amphetamine on lordosis behavior, but the effect of L-amphetamine was only slightly diminished and the action of fenfluramine and p-chloroamphetamine was unaffected. On the other hand, both L- and D-amphetamine-induced stereotype activity was prevented by pimozide treatment. The data suggest that the D-amphetamine effect on lordosis behavior is mediated by increased DA receptor activity. Although it induces stereotype activity by increased DA activity, L-amphetamine, like fenfluramine and p-chloroamphetamine, inhibits the lordosis response by some other action presumably related to serotonergic mechanisms.

Amphetamine↗

Effects of a high-fiber diet and frequent feeding on behavior, reproductive performance, and nutrient digestibility in gestating sows.

A study was conducted to determine the effects of feeding a corn-soybean meal (control) diet vs. a corn-soybean meal-40% soybean hulls (high fiber) diet, as well as the frequency of feeding (once vs. twice daily), on the welfare and performance of gestating sows. Two hundred thirty-nine mixed-parity sows were assigned to a 2 x 2 factorial arrangement of treatments. Sows fed once daily received their entire meal at 0730, whereas sows fed twice daily received one-half of their feed allotment at 0730 and the other half at 1430. The behavior of 68 focal sows (> or = 16 sows per treatment combination) was observed on d 1 postweaning, and on d 40 and d 80 of gestation. The percentage of time standing, lying, sitting, feeding, inactive, and performing stereotypic behaviors was determined. Saliva samples were collected to determine cortisol concentrations. Sow BW and backfat depth were determined on d 0, 40, and 80 of gestation, within 24 h of farrowing, and at weaning. An energy and nitrogen digestibility study was conducted using 36 sows assigned to each of the 4 treatment combinations. Over a 24-h period, the sows fed the high-fiber diet spent less time lying (P < 0.05) than the sows fed the control diet. The frequency of feeding did not affect sow behavior measured over a 24-h period. During mealtimes, sows fed the high-fiber diet spent more time feeding (P < 0.05) than sows fed the control diet. Feeding the high-fiber diet did not affect stereotypic behavior measured over 24 h or during mealtimes. Neither diet nor feeding frequency affected salivary cortisol concentration. Sows fed the high-fiber diet gained less BW and lost backfat (P < 0.05) during gestation compared with sows fed the control diet, whereas sows fed once daily gained less BW and lost backfat (P < 0.05) compared with sows fed twice daily. Sows fed the high-fiber diet had fewer pigs born (P < 0.05) compared with sows fed the control diet. Feeding frequency had no effect on size or weight gain of litters. Sows fed the high-fiber diet exhibited lower digestibility of DM, energy, and N (P < 0.05) compared with sows fed the control diet. Feeding a high-fiber diet utilizing soybean hulls or increasing feeding frequency did not enhance the welfare of sows by reducing stereotypic behaviors nor did it improve reproductive performance.

Animal Feed↗

What children remember about ingroup and outgroup peers: effects of stereotypes on children's processing of information about group members.

Three studies are reported about children's memory for stereotypic behaviors attributed to ingroup and outgroup members. According to research and theory in social cognition, cues present in the situation make cultural representations about group members accessible, and once primed, influence all phases of the information processing sequence. In Study 1, Euro Canadian and Native Canadian children (N=98) recalled stereotypic behaviors attributed to ingroup and outgroup members. In Study 2 (N=87), the influence of individual difference variables was explored. In Study 3 (N=32), the memory of Native Canadian children living on a First Nation reserve for behaviors attributed to ingroup and outgroup members was studied. Biases in recall were found in Studies 1 and 2, but in Study 3, outgroup favoritism, typically found among low status group members, was reversed among children attending a heritage school. Among the individual difference measures examined, age and level of cognitive development predicted what was remembered about group members. Older Euro Canadian children recalled more negative behaviors about outgroup members than did younger children, and more cognitively mature children recognized more information about ingroup than outgroup members. Results were discussed in terms of cognitive and situational factors influencing children's processing of group-relevant information and the challenges children in low status groups face in maintaining a sense of cultural identity.

Child↗

[Rapid and prolonged facilitation of stereotyped motor behavior (verticalization) induced by apomorphine in mice previously submitted to stimulation of dopaminergic receptors].

The climbing behaviour, a stereotyped motor behaviour, is elicited in mice by stimulation of striatal dopamine receptor by low doses of apomorphine. The action of apomorphine is unexpectedly enhanced in animals pretreated with a single dose of this agent (5 mg/kg). This enhancement occurs as early as 2 h following the first administration and persists for at least 3 days. It is also observed after pretreatments with a combination of L-DOPA and dexamphetamine. This effect seems independent from the desensitization of the dopaminergic receptors involved in thermoregulation that we have previously reported.

Animals↗

R(-) and S(+) stereoisomers of 11-hydroxy- and 11-methoxy-N-n-propylnoraporphine: central dopaminergic behavioral activity in the rat.

R(-)11-Hydroxy-N-n-propylnoraporphine (11-OH-NPa) induced stereotyped behavior in the rat as potently (ED50 = 0.80 mg/kg, i.p.) as R(-)apomorphine (APO) and this effect was blocked by haloperidol; the 11-methoxy congener, R(-)11-MeO-NPa, had a weak effect (ED50 greater than 10 mg/kg) and the S(+) isomers had none. The isomer R(-)11-OH-NPa potentiated locomotion stimulated by apomorphine; S(+)11-OH-NPa inhibited it and the isomers of 11-MeO-NPa were inactive. Catecholaporphines usually are inactive orally, but both R(-) and S(+)11-OH-NPa were similarly potent after oral or parenteral administration. The isomer S(+)11-OH-NPa inhibited spontaneous and apomorphine-induced locomotion (ID50 = 1.8-2.7 mg/kg, p.o. and i.p.) and stereotyped behavior (ID50 = 3 mg/kg, p.o. or i.p.), all without inducing catalepsy. While apomorphine was short-acting (1-2 hr), the effects of R(-)11-OH-NPa persisted up to 6-7 hr and those of the S(+) isomer for at least 2.5 hr; moreover, the efficacy of R(-)11-OH-NPa increased markedly up to 3-4 hr, although its ED50 was independent of time (ED50 = 1.7-1.9 mg/kg, i.p. from 1-3 hr). The total effect of R(-)11-OH-NPa (p.o. or i.p.) over time was more than 10-times greater than that of injected apomorphine. These observations accord with the reported high (nM) affinity of 11-OH-NPa at cerebral DA receptor sites (D2 greater than D1) and weak interactions of the 11-methoxy congener. They support the conclusion that the R(-) and S(+) stereoisomers are neuropharmacologically active, respectively, as DA agonist and apparent antagonist, as was found with the enantiomers of N-n-propylnorapomorphine, perhaps due to the low intrinsic postsynaptic agonist activity of the S(+) isomers. Moreover, 11-OH-NPa was highly bioavailable orally and unusually long-acting; it may be absorbed slowly or have active metabolites. Hydroxy-substitution of aporphines at the 11-position, homologous to the 3-OH of DA, evidently is critical for affinity and activity at the DA receptor. These or other monohydroxyaporphines may represent leads to potentially useful DA agonist or antagonist drugs.

Animals↗

Behavioral effects of toxic doses of soman, an organophosphate cholinesterase inhibitor, in the rat: protection afforded by clonidine.

Atropine, a postsynaptic muscarinic antagonist, and clonidine, a presynaptic inhibitor of acetylcholine release, protect mice from the lethal effects of soman, a potent and irreversible cholinesterase inhibitor. The purpose of this study was to determine the effects of atropine (6 mg/kg) and clonidine (0.2 mg/kg) on soman-induced lethality and behavioral changes in the rat. Soman produced a dose-dependent increase in lethality over a narrow concentration range (50-200 micrograms/kg, SC). Soman produced time- and dose-dependent increases in tremor, salivation, hind limb extension, convulsions and chewing behaviors, as well as decreases in three normal stereotyped behaviors, sniffing, locomotion and rearing. Atropine and clonidine were equally effective at limiting soman-induced lethality and behavioral changes. The protective effects of clonidine and atropine were synergistic, even though clonidine antagonizes some of the stereotyped behaviors elicited by atropine. Simultaneous pretreatment with clonidine and atropine completely eliminated the lethality and behavioral changes produced by injection of 200 micrograms/kg soman.

Animals↗

Abnormal behavior.

Farm animals exhibit abnormalities of sexual, maternal, and other social behaviors as well as many stereotyped behaviors. The types and incidence of these abnormal behaviors may depend on the species, its diet, and the environmental conditions under which it is normally maintained. An understanding of the causes of various abnormal behavior patterns will enable the producer and veterinarian to better manage populations of livestock and improve their well-being.

Aggression↗

Extracellular dopamine and amphetamine after systemic amphetamine administration: comparison to the behavioral response.

To further delineate amphetamine-dopamine pharmacokinetic-pharmacodynamic relationships, we examined extracellular levels of dopamine and amphetamine in caudate-putamen after the s.c. administration of 8 mg/kg amphetamine. In a parallel group of animals, we also assessed caudate-putamen tissue levels of the drug. Extracellular concentrations of the transmitter and the drug exhibited similar temporal profiles, each achieving maximum concentrations within 30 min of drug administration. Tissue levels of amphetamine exhibited a similar, although slightly earlier time to maximum levels. The concentrations of amphetamine and dopamine in the extracellular fluid and amphetamine in tissue rapidly declined with similar rates of elimination. In contrast to the temporal profiles for both dopamine and amphetamine, stereotyped behaviors achieved maximum intensity at about 60 min. In addition, although transmitter and drug declined almost 10-fold from maximum values over the 4-hr interval after amphetamine administration, stereotyped behaviors persisted for at least 3 hr before abating. The results of these studies confirm our previous observation that the temporal profiles for stereotyped behaviors and extracellular dopamine are dissociated, and also extend this dissociation to extracellular amphetamine. In addition, although there was a close correspondence between dopamine and amphetamine within each experimental animal, individual animals exhibited a broad range of maximal dopamine responses, suggesting a differential responsiveness to amphetamine.

Amphetamine↗

Differential responses in central dopaminergic activity induced by apomorphine in IPL nude rat.

The IPL nude rat, derived by spontaneous mutation from the Sprague-Dawley strain, presents alterations in the prolactin synthesis and secretion due to an increased dopaminergic inhibition. However, there are no reports concerned to central dopamine activity. The corpus striatum is a brain area involved in the development of stereotyped behavior after the activation of mesolimbic and/or nigro-striatal dopamine pathways. In order to identify possible mesolimbic and/or nigro-striatal dysfunctions in the IPL nude rat, we study the spontaneous oral behaviors and the effects of apomorphine-induced dopaminergic activation on stereotyped behavior and neurochemical changes. Males from both strains were injected with saline or apomorphine (2 and 5 mg/kgs.c.) and evaluated during 30 min in a stereotypes oral tests. The corpus striatum and nucleus accumbens were used to measure dopamine (DA), 3,4-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenylacetic acid (DOPAC) by HPLC. The concentrations were expressed as synthesis rate (DA/DOPA) and turnover rate (DOPAC/DA). We observed that the spontaneous gnaw movements were significantly different between the untreated IPL nude and Sprague-Dawley (SD) rats. Apomophine injection decreased the amount of stereotyped gnawing in IPL nude rats at the two doses used, but it induced an increase in SD rats. Apomorphine also caused an enhancement in the number of biting and sniffing without modifying the licking behavior. In addition, modifications of the dopaminergic activity were also observed. Synthesis rate in the striatum of IPL nude rats was higher than in SD rats after the injection of saline. Apomorphine caused a reduction of the synthesis rate in both strains. Turnover rate was significantly lower in the striatum of IPL nude rats than in the SD rats injected with saline. Apomorphine caused an increase in the turnover rate in both strains. Contrary to observed in the striatum, the 2 mg/kg dose of apomorphine caused a significant increase in the DA synthesis rate in nucleus accumbens, while 5 mg/kg decrease it in both strains. The DA turnover rate in the same area was lower in IPL nude than in SD rats after saline injection. Apomorphine enhances the DA turnover rate in both strains. We conclude that the modifications of the oral spontaneous and induced stereotypical patterns observed in the IPL nude rats could be related to the differential responses in dopaminergic activity in the two brain areas examined.

Animals↗

Behavioral supersensitivity to apomorphine and amphetamine after chronic high dose haloperidol treatment.

Rats administered chronic haloperidol (5 mg/cc) for 2 months exhibited stereotyped gnawing during chronic haloperidol treatment, and after withdrawal from haloperidol, showed significantly greater stereotyped behavior induced by apomorphine or L-amphetamine compared to saline controls. Chronic administration of benztropine mesylate concomitantly with haloperidol reduced the effects of chronic haloperidol on drug induced stereotyped behavior during the withdrawal period.

Amphetamine↗

Does the radial arm maze necessarily test spatial memory?

Since its design 25 years ago (Olton & Samuelson, 1976), the eight-arm radial maze has become very popular and is now widely used to assess spatial memory in rodents. Two versions of the full-baited maze protocol are present in the literature: with or without confinement between the visit of each arm. The confinement was introduced by Olton himself as early as 1977 (Olton, Collison, & Werz, 1977) to eliminate stereotypic behaviors that he had previously observed. It is widely regarded that the confinement prevents rodents from developing these response patterns, and as such it is considered an improved procedure to test spatial memory. Surprisingly, to the best of our knowledge, no study has been especially designed to demonstrate the efficacy of the confinement in blocking the stereotypic behaviors of the animals. The present study compares the strategies of rats trained with or without a confinement procedure. The results show that, after nine days of training, rats submitted to a 5- or a 10-s confinement reach the same level of performance as rats without confinement. The confinement totally prevents stereotypic behaviors like clockwise serial searching strategies which are often observed without confinement. Even a 0-s confinement is sufficient to prevent clockwise strategies, but rats seem to develop other stratagems which do not imply spatial memory. Furthermore, rats previously trained without confinement are unable to perform the task when confinement is introduced on a test day. In contrast, rats previously trained with confinement perform the task correctly when the confinement is no longer present. Thus, without confinement, good levels of performance can be achieved without precise spatial representations.

Animals↗

Changes in spontaneous behavior in the dog following oral administration of L-deprenyl.

An open-field activity test was developed for studying the effect of a single oral dose (range of 0.1-5 mg/kg) of L-deprenyl on spontaneous behavior in the dog. A computer program was used to quantify observations of locomotor activity, directed sniffing, urination, grooming, inactivity, jumping, rearing, and vocalization during a 10-min baseline and posttreatment session. Three dose-dependent behavioral changes were observed: an overall decrease in directed sniffing, an increase in total locomotor activity in females, and a decrease in frequency of urination in males. These effects were only seen at the dose levels of 2 mg/kg or higher. Computer-assisted tracings of behavioral patterns showed increased stereotypical behavior and decreased exploratory behavior at the high-dose levels. These behavioral effects are most likely due to either increased levels of phenylethylamine resulting from inhibition of monoamine oxidase B and/or the production of amphetamines as a result of the metabolism of L-deprenyl.

Aging↗

Neuromuscular patterns of stereotypic hindlimb behaviors in the first two postnatal months. III. Scratching and the paw-shake response in kittens.

Neuromuscular patterns of scratching and the paw-shake response were studied in normal kittens from birth to postnatal day 60. Onset of both behaviors coincided with the development of secure weight-bearing posture and occurred on postnatal day 21 for scratching and postnatal day 26 for paw shaking. At onset, cycle periods for scratching (5-6 Hz) and paw shaking (8-10 Hz) were similar to that for adult cats, and EMG patterns were adult-like. The scratch cycle consisted of reciprocal flexor and extensor bursts of equal duration, while the shake cycle consisted of coactive knee extensor and ankle flexor bursts alternately active with ankle extensor bursts. The lack of scratching and paw shaking during the first 3 postnatal weeks and the adult-like EMG patterns at onset are consistent with the hypothesis that pattern-generating circuits within lumbosacral segments are available early in development but inhibited by the rostral neuraxis until postural control is sufficient to accommodate the response. To eliminate rostral inputs, including descending input critical for postural control, kittens were spinalized at the T12 level, and onset of paw shaking was accelerated. In kittens spinalized at birth, paw-shake onset occurred on postnatal day 14, while in kittens spinalized on postnatal day 14, onset occurred 48 h after spinalization. In all spinal kittens, however, knee extensor activity was disrupted and not normal by postnatal day 60. Mature neuromuscular patterns for scratching and paw shaking are available at onset of the behavior during normal development. Spinalization hastens the onset of paw shaking but the normal neuromuscular synergy is disrupted as well as the temporal structure of the multi-cycle response. Disruptions following spinalization may be due to altered development of spinal pattern generators or aberrant feedback from atypical hindlimb motions due to a retardation of hindlimb growth and an alteration of muscle contractile properties in spinal kittens.

Age Factors↗

Neuromuscular patterns of stereotypic hindlimb behaviors in the first two postnatal months. I. Stepping in normal kittens.

Neuromuscular patterns associated with the development of hindlimb stepping behaviors were studied from birth to postnatal day 60 in normal kittens. Hindlimb muscles were chronically implanted with EMG electrodes at birth to characterize interlimb coordination and intralimb synergies during development of overground and treadmill stepping. Airstepping was also examined but seldom occurred after the second postnatal week. All kittens performed stepping under each condition, including weight-supported stepping, by postnatal day 3. The number of sequential steps on the treadmill and overground increased with age and cycle periods decreased. At onset, stepping behaviors were characterized by adult-like EMG patterns. Interlimb coordination was typified by alternating extensor bursts of similar duration. Extensors at the knee and ankle were coactive during the stance phase, and extensor burst durations were strongly correlated with the cycle periods over a wide range of stepping frequency. Ankle flexor and extensor muscles were reciprocally active during postural tremor, bouts of airstepping, and weight-supported steps on the treadmill and overground. The duration of the reciprocal flexor bust did not vary with cycle period or age. Observations of stepping behaviors and adult-like EMG patterns during initial postnatal development were contingent on optimal testing conditions. Taken together, the data suggest that pattern-generating circuits for regulating interlimb coordination and intralimb muscle synergies are potentially functional prior to the normal ontogenetic onset of locomotion. Perhaps the prolonged postnatal development of locomotion reflects the time required to establish adaptive mechanisms, such as postural control and agility, rather than spinal pattern-generating circuits for locomotion.

Animals↗

Gonadectomy and sex differences in the behavioral responses to amphetamine and apomorphine of rats.

Following treatment with 5 mg/kg d-amphetamine sulfate or 2 mg/kg apomorphine hydrochloride female rats displayed more intense and longer lasting stereotyped behavior than males. Gonadectomy did not affect the display of stereotyped behavior induced by either drug in either sex. A lower dose of amphetamine (1 md/kg) caused greater stimulation of locomotor activity in females than in males. Castration of males had no effect, but ovariectomy blocked the stimulating effect of amphetamine on activity. By contrast, low doses of apomorphine depressed activity in a dose-dependent manner that was somewhat greater in ovariectomized females than in the other groups. These data add to the growing body of literature demonstrating that gonadal hormones modulate the activity of brain dopamine systems.

Amphetamine↗