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PubMed1995

Alterations in local cerebral glucose utilization in rats after chronic amphetamine administration without subsequent challenge.

The 2-deoxyglucose (2-DG) method was used to study regional metabolic changes in rats following chronic d-amphetamine treatment without subsequent challenges. Four groups of rats were pretreated (intraperitoneal administration) with d-amphetamine (0, 1, 5, or 10 mg/kg) once per day for 14 days. After a 7-day abstinence period without further challenge, the 2-DG method was used to measure the rates of local cerebral glucose utilization (LCGU). Significant metabolic changes among the four groups were found in five brain regions, including the nucleus accumbens and the lateral habenular nucleus. Another four groups of rats with the same pretreatment regimens, challenged with 5 mg/kg d-amphetamine, were used for behavioral testing. The results showed intense stereotyped behaviors in the 5 mg/kg and the 10 mg/kg groups. In the steady state, however, there were no significant glucose utilization changes in the nigrostriatal system, which is thought to be related to stereotyped behaviors. During steady state, metabolic changes were found in a limited number of brain regions. No difference in LCGU was found in the sensitization-related regions. Further challenges with stimulants may be necessary to investigate the metabolic responses after sensitization.

Animals↗
PubMed2004

Efficacy of fluvoxamine as a treatment for behavioral symptoms in frontotemporal lobar degeneration patients.

Patients with frontotemporal lobar degeneration (FTLD) present a profound personality change, social misconduct, overeating, and stereotyped behavior. We examined the hypothesis that many of the behavioral symptoms of FTLD will respond to selective serotonin reuptake inhibitors (SSRIs). Sixteen FTLD patients were treated with an SSRI (fluvoxamine maleate) in an open 12-week trial. Treatment responses for stereotyped behavior and other neurobehavioral symptoms were evaluated by the Stereotypy Rating Inventory and the Neuropsychiatric Inventory. The behavioral symptoms, especially stereotyped behaviors of FTLD, significantly improved after treatment. Randomized, placebo- and other SSRI-controlled trials may improve available treatments.

Aged↗
PubMed2001

A survey assessment of variables related to stereotypy in captive giraffe and okapi.

Stereotypic behavior has been investigated in a wide variety of animals, but little published information is available on this problem in captive exotic ungulates. A survey was used to gather information on the prevalence of stereotypic behavior in giraffe and okapi and to identify variables associated with these behaviors. Of the 71 institutions that received a survey, 69.0% responded. Data were reported for 257 individuals, including 214 giraffe (representing five subspecies) and 29 okapi. Of the animals included in the survey, 79.7% performed at least one type of stereotypic behavior. Licking of non-food objects (72.4%) and pacing (29.2%) were the most prevalent stereotypic behaviors, though other stereotypies were reported in 3.2% of the animals. The results of a logistic regression performed on the data indicated that sub species, number of hours the individuals spent indoors, access at night to conspecifics, feeding frequency, method of feeding, and type of food provided were predictors of stereotypic licking. Sub species, birth history, size of the indoor enclosure, environmental change, and type of food provided were found to be significant predictors of stereotypic pacing. In general, feeding motivation appears to be related to an oral stereotypy, whereas other environmental factors appear to be associated with a locomotor stereotypy. The results of this study suggest changes in management strategies that may be empirically studied and applied to improve the well-being of captive populations of giraffe and okapi.

Journal Article↗
PubMed1984

The effect of a single administration of phencyclidine on behavior in the rat over a 21-day period.

The effects of phencyclidine (PCP) (7.0, 11.7, 19.5, 32.6, and 54.4 mg/kg) on locomotor activity, stereotyped behavior (circling, backing up, and weaving frequency), and rotarod performance were evaluated. In addition, the frequency of other PCP-induced abnormal behaviors (head in corner, arched back, and cataleptic freeze) was determined. All doses of PCP produced a significant increase in locomotor activity and stereotyped behavior as well as an impairment of rotarod performance. Both the duration and the time to peak effects (with the exception of rotarod performance) of these PCP-induced behavioral changes appeared to be dose dependent. The delay in attaining peak effects for locomotor activity and stereotypy was attributed to PCP-induced gross motor ataxia, which became more severe and long lasting with increasing dose. Although the longest period of time that significant changes were seen in locomotor activity, stereotyped behavior, and rotarod performance was 12 hr, sporadic recurrences of stereotypy and a significant increase in cataleptic freeze were observed in the high-dose groups (19.5, 32.6, and 54.4 mg/kg) up to 21 days postadministration. These persistent behaviors (stereotypy and cataleptic freeze) are not unlike certain of the prolonged behaviors seen in man with PCP overdose (catatonic stupor along with repetitive orofacial and limb movements).

Animals↗
PubMed2002

Effects of long-term moderate alcohol consumption on agonistic and affiliative behavior of socially housed female cynomolgus monkeys (Macaca fascicularis).

RATIONALE: The most widely used drug in the US is alcohol. Most people who use alcohol are light-to-moderate drinkers. One or two drinks/day is thought to be not only safe but potentially health-promoting. However, little is known about the chronic effects of moderate alcohol consumption. Alcohol, even in moderate doses, has immediate and robust effects on behavior. OBJECTIVE: To determine the effects of long-term moderate alcohol consumption on the social interactions of adult monkeys. METHODS: Forty-nine adult, ovariectomized monkeys lived in small, stable social groups for 31 months and voluntarily consumed a 2-drink/day equivalent (0.5 g/kg ethanol), 5 days/week for 24 months. Alcohol was presented in a sweet tasting non-nutritive vehicle to half the monkeys, while the other half received vehicle plus maltose-dextrin isocalorically substituted for alcohol. Social behavior was recorded 1 h before, 1 h after, and 5 h after alcohol. RESULTS: Alcohol caused chronic changes in aggressive and affiliative behavior that were not dependent upon the presence of circulating alcohol. Alcohol increased physical aggression. A subset of the animals was at higher risk for alcohol-induced physical aggression. Alcohol decreased positive affiliative behaviors, increased time spent alone, and increased the frequency of extragroup vigilance. Acutely, alcohol increased the rate of behavioral pathology, i.e. stereotypic behaviors, such as hair plucking, which are normally observed only under adverse environmental conditions. CONCLUSIONS: Long-term moderate alcohol consumption caused chronic deleterious changes in the social interactions of primates in small, stable social groups. These data suggest that chronic moderate alcohol consumption can compromise optimal social interactions in primate species, including human beings.

Aggression↗
PubMed1985

[Chronological change in abnormal behavior produced by long-term methamphetamine administration in the rat].

Rats received once daily injections of methamphetamine (MAP; 4 mg/kg/day) intraperitoneally, at most 100 times. Enhanced ambulatory activity by MAP reduced during the long-term administration of MAP. The mean rating score of MAP-induced abnormal behavior, including locomotion, stereotyped behavior, motor inhibition and the response to acoustic stimulation, increased until 56th injection of MAP. But after that, the score tended to decrease mainly because the injected MAP failed to keep the movement of rats reduced under acoustic stimulation. Neither the time course of these rating score nor the decrease in [3H] spiperone binding sites, examined after the injection of MAP 100 times, seemed to develop along with the repeated MAP administration. Thus, the changes in both behavior and [3H] spiperone binding sites produced by repeated MAP would not necessarily indicate the symptoms of MAP-induced psychosis in man, because the susceptibility to psychosis in man increases along with the time of MAP injection. It is presumed that the animal model of psychosis produced by administration of MAP is important not as a model of psychotic symptoms, but as a model of increased susceptibility to psychosis induced by MAP.

Animals↗
PubMed1984

Episodic excitation and changes in aggressive behavior induced by apomorphine in rats subjected to REM sleep deprivation.

Behavioral changes induced by apomorphine in normal, pseudodeprived (control) and REM sleep-deprived AM-2/TOR inbred rats were investigated. Deprived rats exhibited aggressive behavior for nearly 30 min in the absence of administration of drug, this effect not being observed in normal or control rats. The administration of apomorphine (1, 2 and 5 mg/kg) 5 min before the test elicited short periods of aggressive behavior in normal and control rats, but decreased the total duration of aggressive behavior in deprived rats. However, the deprived rats exhibited a more intense aggressive behavior, since the frequency of real fighting events was enhanced. The administration of apomorphine to deprived rats elicited stereotyped behavior. Enhancement of stereotyped behavior by increasing the dose was correlated with a reduction in the duration of aggressive behavior. Apomorphine also induced short episodes of intense excitability, manifested by increased locomotor activity, jumping and vocalization. This behavioral response was termed "episodic excitation". Deprived rats were significantly more sensitive to apomorphine-induced episodic excitation than normal and control rats. The episodic excitation, stereotyped and aggressive behavior displayed by deprived rats, injected with apomorphine, alternated with time. The results demonstrate increased responsiveness to apomorphine after deprivation of REM sleep. The possible mechanism for such interaction is discussed.

Aggression↗
PubMed1994

Effects of risperidone on phencyclidine-induced behaviors: comparison with haloperidol and ritanserin.

In this study, we investigated whether risperidone, a serotonin-S2A (5-HT2A)/dopamine-D2 (D2)-receptor antagonist, inhibits phencyclidine (PCP)-induced stereotyped behaviors in comparison with haloperidol and ritanserin. Moreover, we also attempted to investigate the effects of these antipsychotics on the contents of dopamine, serotonin (5-HT) and their metabolites in rat striatum and frontal cortex. In rats, PCP (5 mg/kg, i.p.) caused hyperlocomotion and stereotyped behaviors, including sniffing, head-weaving, backpedalling and turning. Both resperidone (0.8-2.4 mg/kg, p.o.) and haloperidol (0.3-1.0 mg/kg, p.o.) inhibited these behaviors, except for backpedalling, in a dose-dependent manner. PCP (10 mg/kg, i.p.) produced hyperlocomotion and stereotyped behaviors, including rearing, sniffing head-twitch, backpedalling and turning. Risperidone (0.8-2.4 mg/kg, p.o.) inhibited both hyperlocomotion and PCP-induced behaviors, except for backpedalling, while ritanserin (3-10 mg/kg, p.o.) inhibited only the head-twitch. These results suggest that risperidone may have an antipsychotic effect on schizophrenia as well as PCP psychosis in humans by exerting a mixed 5-HT2A/D2 antagonism. Neurochemically, the increasing effects of risperidone on the content of DOPAC and the ratio of DOPAC to dopamine in the striatum were lower than those of haloperidol. These findings may support the view that the extrapyramidal side effects of risperidone are lower than those of haloperidol in clinical situations.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Biphasic effects of MIF-1 and Tyr-MIF-1 on apomorphine-induced stereotypy in rats.

The effects of several doses of MIF-1 and Tyr-MIF-1 (0.2, 0.5, 1.0 and 5.0 mg/kg, SC) on the stereotypic behavior induced by various doses (0.08, 0.2, 0.5, 1.0 and 2.0 mg/kg, SC) of apomorphine (APO) were tested in rats. MIF-1 increased the stereotypic behavior induced by 0.5 and 1.0 mg/kg of APO, but decreased the stereotypic behavior induced by 2.0 mg/kg of APO. Tyr-MIF-1 showed a biphasic effect similar to that exerted by MIF-1. The results suggest that the type of response to MIF-1 and Tyr-MIF-1 after APO is influenced by the activity of central dopaminergic neurons.

Animals↗
PubMed1988

Effect of hand splints on stereotypic hand behavior of three girls with Rett syndrome.

The purpose of this multiple baseline study was to examine the effect of bilateral hand splints on the persistent stereotypic hand movements of three adolescent girls with Rett syndrome. Among the most characteristic features of Rett syndrome are stereotypic hand-writing and hand-biting behavior and loss of previously acquired functional hand skills. The hand splints used in this study consisted of cuffs encircling the palm that positioned the subjects' thumbs in abduction. Duration percentages of subjects' stereotypic hand behavior and functional hand use were calculated from five-minute videotaped segments recorded during a finger-feeding condition and a free-time condition. All three subjects demonstrated a decrease in the amount of time spent in stereotypic hand behavior after application of hand splints, and one subject showed an increase in finger-feeding skills while wearing hand splints. Limitations of the study are discussed, and suggestions for clinical application and future research are offered.

Adolescent↗
PubMed2005

Genotoxic, neurotoxic and neuroprotective activities of apomorphine and its oxidized derivative 8-oxo-apomorphine.

Apomorphine is a dopamine receptor agonist proposed to be a neuroprotective agent in the treatment of patients with Parkinson's disease. Both in vivo and in vitro studies have shown that apomorphine displays both antioxidant and pro-oxidant actions, and might have either neuroprotective or neurotoxic effects on the central nervous system. Some of the neurotoxic effects of apomorphine are mediated by its oxidation derivatives. In the present review, we discuss recent studies from our laboratory in which the molecular, cellular and neurobehavioral effects of apomorphine and its oxidized derivative, 8-oxo-apomorphine-semiquinone (8-OASQ), were evaluated in different experimental models, i.e., in vitro genotoxicity in Salmonella/microsome assay and WP2 Mutoxitest, sensitivity assay in Saccharomyces cerevisiae, neurobehavioral procedures (inhibition avoidance task, open field behavior, and habituation) in rats, stereotyped behavior in mice, and Comet assay and oxidative stress analyses in mouse brain. Our results show that apomorphine and 8-OASQ induce differential mutagenic, neurochemical and neurobehavioral effects. 8-OASQ displays cytotoxic effects and oxidative and frameshift mutagenic activities, while apomorphine shows antimutagenic and antioxidant effects in vitro. 8-OASQ induces a significant increase of DNA damage in mouse brain tissue. Both apomorphine and 8-OASQ impair memory for aversive training in rats, although the two drugs showed a different dose-response pattern. 8-OASQ fails to induce stereotyped behaviors in mice. The implications of these findings are discussed in the light of evidence from studies by other groups. We propose that the neuroprotective and neurotoxic effects of dopamine agonists might be mediated, in part, by their oxidized metabolites.

Animals↗
PubMed1994

Home cage behavior of rhesus monkeys with long-term deficiency of omega-3 fatty acids.

In an observational study with a blind observer, rhesus monkeys deficient in omega-3 (omega-3 or n-3) fatty acids initiated more bouts of stereotyped behavior in their home cages than monkeys fed a matched control diet abundant in omega-3 fatty acids. Locomotion bouts were also more frequent in deficient monkeys, but nonstereotyped locomotion did not differ. Both stereotyped behavior and the sum of all behavioral bouts were more frequent in 4-5-year-old than in 2-3-year-old monkeys, and stereotype decreased after meals in males but not females. The stereotyped behaviors associated with a deficit in omega-3 fatty acids were those typical of rhesus monkeys raised as partial social isolates or those whose surroundings have been disrupted.

Aging↗
PubMed2004

The bombesin/gastrin releasing peptide receptor antagonist RC-3095 blocks apomorphine but not MK-801-induced stereotypy in mice.

Bombesin (BN)-like peptides might be involved in the pathogenesis of neuropsychiatric disorders such as schizophrenia. Stereotyped behaviors induced by the dopamine receptor agonist apomorphine or the N-methyl-D-aspartate glutamate receptor antagonist dizocilpine (MK-801) in rodents have been proposed as animal models of schizophrenic psychosis. In the present study we evaluated the effects of the BN/gastrin-releasing peptide receptor (GRP) antagonist (D-Tpi6, Leu13 psi[CH2NH]-Leu14) bombesin (6-14) (RC-3095) on apomorphine and MK-801-induced stereotyped behavior in mice. An intraperitoneal (i.p.) injection of RC-3095 (1.0, 10.0 or 100.0 mg/kg) blocked apomorphine-induced stereotypy. The inhibitory effect of RC-3095 on apomorhine-induced stereotypy was similar to that induced by haloperidol (0.5 mg/kg). RC-3095 did not affect stereotyped behavior induced by MK-801 (0.5 mg/kg). The results provide the first evidence that BN/GRP receptor antagonism blocks stereotyped behavior induced by a dopamine agonist. Together with previous evidence, the present study indicates that the BN/GRP receptor can be considered a drug target in the investigation of potential new agents for treating neuropsychiatric disorders.

Animals↗
PubMed1991

Sensitization of amphetamine-stereotypy reduces plasma corticosterone: implications for stereotypy as a coping response.

The potential coping functions of amphetamine-induced stereotypy were investigated using a physiological index of stress or arousal, plasma corticosterone level. A series of five injections of d-amphetamine was used to enhance stereotyped behavior in control animals as well as in rats with bilateral dopamine-depleting lesions of the caudate-putamen. This regimen of amphetamine injections significantly increased stereotyped behavior and also reduced the normal elevation in corticosterone produced by treatment with d-amphetamine. This effect was apparent in both control and lesioned animals. These results support the hypothesis that amphetamine-induced stereotyped behavior functions to reduce stress or arousal and additionally suggest that this effect is largely independent of underlying dopaminergic mechanisms.

Adaptation, Psychological↗
PubMed1986

Behavior performed at onset of drug action and apomorphine stereotypy.

This study tests the hypothesis that stereotyped behavior induced by apomorphine reflects strengthening of behavior observed at the onset of drug action. Rats (n = 26) were injected with apomorphine (1.25 mg/kg) while being engaged in copulation. Contrary to the hypothesis, apomorphine did not strengthen ongoing copulation but arrested it. Instead of mating the males became engaged in behavior typically exhibited by rats injected with the drug. It is speculated that stereotyped behavior may be an expression of a drug-induced shift of attention or responsiveness to some particular range of stimuli.

Animals↗
PubMed1989

Are antagonists of dopamine D1 receptors drugs that attenuate both positive and negative symptoms of schizophrenia? A pilot study in Java monkeys.

Amphetamine is known to elicit stereotyped behavior in various species. For a long time, this effect was considered to be an animal model for the positive symptoms of schizophrenia. In addition, amphetamine is known to induce a strong social isolation in socially living monkeys. Both on symptomatologic and pharmacologic grounds, this amphetamine-induced social isolation has been suggested to represent an animal model for the negative symptoms of schizophrenia. To date no effective treatment has been found for these negative symptoms. We now report that the selective D1 dopamine antagonist SCH 23390 is very effective in antagonizing both the stereotyped behavior and the social isolation in Java monkeys induced by amphetamine. Moreover, SCH 23390 is able to reinstate normal behavior in these animals. These results may have important consequences for our understanding of the functional significance of the D1 receptor as well as for the clinical treatment of the positive and negative symptoms of schizophrenia.

Animals↗