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PubMed1979

Severe impairments of social interaction and associated abnormalities in children: epidemiology and classification.

The prevalence, in children aged under 15, of severe impairments of social interaction, language abnormalities, and repetitive stereotyped behaviors was investigated in an area of London. A "socially impaired" group (more than half of whom were severely retarded) and a comparison group of "sociable severely mentally retarded" children were identified. Mutism or echolalia, and repetitive stereotyped behaviors were found in almost all the socially impaired children, but to a less marked extent in a minority of the sociable severely retarded. Certain organic conditions were found more often in the socially impaired group. A subgroup with a history of Kanner's early childhood autism could be identified reliably but shared many abnormalities with other socially impaired children. The relationships between mental retardation, typical autism, and other conditions involving social impairment were discussed, and a system of classification based on quality of social interaction was considered.

Adolescent↗

PubMed1977

Variability in development of tolerance to repeated injections of low doses of dl-amphetamine in rats.

Male albino rats received injections of saline for 5 days before and 5 days after a series of 10 daily injections of dl-amphetamine, 1 or 5 mg/kg, sc. Core temperatures were measured every 30 min for 4 h after each injection and feeding activity (on a CRF operant schedule) every 30 min throughout. After amphetamine at either 0800 or 2000 h, a dose-related hyperthermia, stereotypic behavior, and an initial inhibition of feeding occurred. This anorexia decreased over the 4-h post injection period only in the evening-injected rats receiving 5 mg/kg. Mean body weights of all groups continued to increase during amphetamine administration. Mean 24-h food intake tended to remain below that in the control period and the hyperthermic response did not change significantly in any group. Initially on withdrawal from amphetamine all groups showed 'rebound' feeding. Taken with earlier reports, these results suggest that tolerance development to amphetamine-induced anorexia, hyperthermia, and stereotypic behavior occurs at different rates and is dependent upon frequency, route, dose, time, the amphetamine used, and whether the diet was restricted.

Amphetamine↗

PubMed1981

Antagonism of hypothermia and behavioral response to apomorphine: a simple, rapid and discriminating test for screening antidepressants and neuroleptics.

The antagonism of hypothermia induced by two doses of apomorphine (1 to 16 mg/kg) is proposed as an improved screening test for both neuroleptics and antidepressants. Low dose apomorphine-induced hypothermia (1 mg/kg) differentiates sulpiride-like neuroleptics (which better antagonize this effect of apomorphine than other effects such as stereotyped behavior) from haloperidol-like drugs. The latter equally antagonize the two effects of apomorphine. The effects of sulpiride are also distinct from those of chlorpromazine-like drugs which strongly antagonize stereotyped behavior, but not hypothermia induced by apomorphine. Hypothermia induced by a high dose of apomorphine (16 mg/kg) is not antagonized by neuroleptics, but is strongly antagonized by antidepressants (imipramine-like drugs, amineptine, amoxapine, nomifensine, viloxazine) and potential antidepressants (beta-adrenergic stimulants). The use of these two tests rapidly screens both antidepressants and neuroleptics and classifies neuroleptics according to their profile of action on the dopaminergic system.

Animals↗

PubMed1984

Sex-dependent differences in the pharmacological actions and pharmacokinetics of phencyclidine in rats.

This study was designed to assess the sex differences in phencyclidine(PCP)-induced ambulatory activity in an open-field, stereotyped behaviors, motor incoordination, tremor, salivation, the regional and subcellular distributions of PCP in the brain and the half-life of PCP in the brain and plasma. Female rats appeared to be more sensitive to PCP as evidenced by hyperactivity, stereotyped behaviors, motor incoordination, tremor, salivation and ataxia. The concentrations of PCP in female rat brain were higher than in the male rats in some discrete brain areas and subcellular fractions. The half-life of PCP in the brain and plasma was longer in female rats than in male rats. The inverse relationship of pharmacological responses to PCP and biotransformation of PCP in both sexes of rats suggests that sex differences in pharmacological actions of PCP depend largely on differences in ability to biotransform the drug.

Animals↗

PubMed1986

D-2 dopamine receptor synthesis and turnover in rat striatum.

Direct injection of phenoxybenzamine into rat striatum inhibited apomorphine-induced stereotyped behavior. This inhibition corresponded well with the inhibition of D-2 dopamine receptor labelling with [3H]spiroperidol. Both the behavioral response and the receptor level were completely restored within 5 days after the injection. The recoveries of both were blocked by cycloheximide. The rate of synthesis and half-life of the D-2 receptor associated with the stereotyped behavior were calculated to be 6.9 fmol/mg protein per h and 28 h, respectively.

Animals↗

PubMed2006

Prenatal cocaine dampened behavioral responses to methylphenidate in male and female adolescent rats.

Clinical and animal data point toward deficits in attention and arousal after prenatal cocaine exposure. Since methylphenidate (MPD) is widely used to treat attention disorders, we wanted to determine whether prenatal cocaine (PC) exposure affects the behavioral response to MPD in young rats of both sexes. Pregnant dams received 60 mg/kg of cocaine or vehicle from gestational days 8-22 by intragastric intubations. After delivery, litters were culled to 10 (5 males, 5 females) and fostered. On a single day between PND 41-44 locomotion was recorded in a Plexiglas box within an Accuscan activity monitor after receiving a single injection of 10 mg/kg intraperitoneally of MPD or saline. Rats were also videotaped for analysis of stereotyped behavior. Results showed that MPD administration enhanced locomotion compared to saline injected groups. PC exposure in male rats did not have any effect on the locomotor response to MPD compared to prenatal controls. However, PC-exposed males showed a lower amount of time spent in low intensity stereotypy compared to prenatal control males and both groups of females that received MPD. PC exposure in female rats that received MPD dampened the locomotor response compared to prenatal control females that also received MPD. In conclusion PC exposure dampens the behavioral response to MPD differentially in males and females with an apparent selectivity of locomotion in females and stereotyped behavior in males.

Animals↗

PubMed1988

Behavioral differences in the developing rat following postnatal anoxia or postnatally injected AF-64A, a cholinergic neurotoxin.

Rat pups were submitted postnatally to one of two procedures: a 25-min exposure to 100% nitrogen or an i.c.v. bilateral injection of AF-64A, 2 nmol contained in 1-microliter saline. Throughout further development of either group, their performance in passive and active avoidance tests and in amphetamine-induced stereotype behavior was followed and compared. Both groups exhibited hyperactivity which persisted until 42 days of age in the anoxia group and beyond 120 days in the AF-64A group. Both groups were equally inferior to controls in the passive avoidance test, but only the anoxia group was inferior to controls in the active avoidance test. Amphetamine-induced stereotype behavior was much less pronounced in the anoxia group relative to AF-64A-treated rats or to controls. The results suggest that the lesion induced by the neurotoxin is more specific and less widespread than the one caused by anoxia.

Animals↗

PubMed1984

[Studies on the reverse tolerance phenomenon after repeated methamphetamine treatment in rats].

Male rats of the Wistar strain were divided into three groups, to which three different doses of methamphetamine (MAP), 0.5 mg, 2 mg, and 4 mg/kg/day, respectively, were intraperitoneally administered 5 times per week for 36 days. Stereotyped behaviors were scored according to the method of Ellinwood & Balster. During the period of repeated MAP treatment, these behaviors increased in a dose dependent manner. Group I treated with 0.5 mg/kg of MAP demonstrated more prominently an increased sensitivity to MAP than the other two, Group II with 2 mg/kg and Group III with 4 mg/kg. Following the withdrawal period of 4 weeks, the rats were reinjected with 0.5 mg/kg of MAP. They showed higher scores of stereotypies than those treated acutely with MAP, that is, reverse tolerance for MAP was observed, although this phenomenon was not necessarily observed in a dose dependent manner for each variable of the behaviors. Lethal autonomic response was observed in Group I and II, in which animals appeared to have reverse tolerance for autonomic response to MAP reinjection in contrast to in Group III. It can be concluded that repeated administration of MAP induces stereotyped behaviors in a dose dependent manner, while autonomic response is not likely to form tolerance.

Animals↗

PubMed2002

Impact of descending brain neurons on the control of stridulation, walking, and flight in orthoptera.

Orthopteran insects (crickets, bushcrickets, and acridid grasshoppers) are preferred preparations for the study of the central nervous mechanisms that underlie behavior. Many of their behaviors are based on central rhythm-generating circuits located in the ganglia of the ventral nerve cord. Activities of these circuits must be coordinated and adapted to the behavioral context by sensory information, which can derive from proprioceptive or exteroceptive inputs. Information from various sensory modalities converges in yet unidentified "higher brain centers" that integrate and transform it into activity patterns across populations of descending brain neurons (DBNs). Transmission of "decisions" to the thoracic motor centers leads to adjustment of their functions in order to fit the sensory situation encountered. A number of unique DBNs has been identified by morphological and physiological criteria and their role in controlling aspects of specific behaviors has been the subject of various studies. Their functions range from "switch-like" transmitters of brain output to complex integration units for sensory inputs of various modalities and their appropriate insertion into the ongoing activities of the thoracic rhythm generators. This paper highlights some of the characteristics of DBNs by focussing on three motor behaviors: stridulation, a stereotyped behavior that seems to be mainly controlled by command-like DBNs; walking, a plastic behavior whose various parameters must continuously be adjusted to a changing sensory environment; and flight, in which the information for course corrections encoded for by different types of DBNs is transformed to match the rhythmic activity of the flight oscillators before it affects the respective motoneurons.

Animals↗

PubMed2001

Chronic inositol increases striatal D(2) receptors but does not modify dexamphetamine-induced motor behavior. Relevance to obsessive-compulsive disorder.

A large body of evidence suggests that the neuropathology of obsessive-compulsive disorder (OCD) lies in the complex neurotransmitter network of the cortico-striatal-thalamo-cortical (CSTC) circuit, where dopamine (DA), serotonin (5HT), glutamate (Glu), and gamma-amino butyric acid (GABA) dysfunction have been implicated in the disorder. Chronic inositol has been found to be effective in specific disorders that respond to selective serotonin reuptake inhibitors (SSRIs), including OCD, panic, and depression. This selective mechanism of action is obscure. Since nigro-striatal DA tracts are subject to 5HT(2) heteroreceptor regulation, one possible mechanism of inositol in OCD may involve its effects on inositol-dependent receptors, especially the 5HT(2) receptor, and a resulting effect on DA pathways in the striatum. In order to investigate this possible interaction, we exposed guinea pigs to oral inositol (1.2 g/kg) for 12 weeks. Subsequently, effects on locomotor behavior (LB) and stereotype behavior (SB), together with possible changes to striatal 5HT(2) and D(2) receptor function, were determined. In addition, the effects of chronic inositol on dexamphetamine (DEX)-induced motor behavior were evaluated. Acute DEX (3 mg/kg, ip) induced a significant increase in both SB and LB, while chronic inositol alone did not modify LA or SB. The behavioral response to DEX was also not modified by chronic inositol pretreatment. However, chronic inositol induced a significant increase in striatal D(2) receptor density (B(max)) with a slight, albeit insignificant, increase in 5HT(2) receptor density. This suggests that D(2) receptor upregulation may play an important role in the behavioral effects of inositol although the role of the 5HT(2) receptor in this response is questionable.

Animals↗

PubMed2000

Methamphetamine-induced striatal dopamine release, behavior changes and neurotoxicity in BALB/c mice.

The behaviors associated with the neurotoxic effects of methamphetamine were evaluated in BALB/c mice. Hyperthermia and behavioral observations were measured 60 min after each subcutaneous injection of methamphetamine (4x4 or 8 mg/kg) or saline, each given 2 h apart. The behavioral observations included stereotyped behaviors, incidence of hemorrhage in breast, salivation and self-injurious behavior (SIB). Repeated administration of methamphetamine produced these behavioral changes and hyperthermia, but resulted in hypothermia by the final injection (8 mg/kg). In addition, the methamphetamine treatment induced a long-lasting dopamine depletion of similar magnitude in the 4 and 8 mg/kg-treated animals. In a time course study striatal monoamine levels were measured 60 min after each injection of these doses. The first and second injections of methamphetamine (8 mg/kg) produced a drastic increase in striatal 3-methoxytyramine; this failed to occur after the third or fourth injection of the same dose. In contrast, 4 mg/kg of methamphetamine also produced an increase in 3-methoxytyramine after the second and third injections of the drug and, in this case, these were maintained for the duration of the treatment. Striatal 3, 4-dihydroxyphenylacetic acid levels also drastically decreased following both doses of methamphetamine, suggesting inhibition of monoamine oxidase in striatum. Moreover, a single injection of methamphetamine increased striatal 2,3-dihydroxybenzoic acid formation. These results suggest that the incidence of hyperthermia, SIB and striatal dopamine neurotoxicity are closely linked to striatal dopamine release and inhibition of monoamine oxidase produced by methamphetamine in BALB/c mice.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Signal transduction in eclosion hormone-induced secretion of ecdysis-triggering hormone.

Inka cells of insect epitracheal glands (EGs) secrete preecdysis and ecdysis-triggering hormones (PETH and ETH) at the end of each developmental stage. Both peptides act in the central nervous system to evoke the ecdysis behavioral sequence, a stereotype behavior during which old cuticle is shed. Secretion of ETH is stimulated by a brain neuropeptide, eclosion hormone (EH). EH evokes accumulation of cGMP followed by release of ETH from Inka cells, and exogenous cGMP evokes secretion of ETH. The secretory responses to EH and cGMP are inhibited by the broad-spectrum kinase inhibitor staurosporine, and the response to EH is potentiated by the phosphatase inhibitor calyculin A. Staurosporine did not inhibit EH-evoked accumulation of cGMP. Changes in cytoplasmic Ca2+ in Inka cells during EH signaling were monitored via fluorescence ratioing with fura-2-loaded EGs. Cytoplasmic Ca2+ increases within 30-120 s after addition of EH to EGs, and it remains elevated for at least 10 min, corresponding with the time course of secretion. Secretion is increased in dose-dependent manner by the Ca2+-ATPase inhibitor thapsigargin, a treatment that does not elevate glandular cGMP above basal levels. The secretory response to EH is partially inhibited in glands loaded with EGTA, while cGMP levels are unaffected. These findings suggest that EH activates second messenger cascades leading to cGMP accumulation and Ca2+ mobilization and/or influx and that both pathways are required for a full secretory response. cGMP activates a staurosporine-inhibitable protein kinase. We propose that Ca2+ acts via a parallel cascade with a time course that is similar to that for cGMP activation of a cGMP-dependent protein kinase.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1978

Effective treatment of self-injurious behavior through a forced arm exercise.

A forced arm exercise was investigated as a means of eliminating head-hitting in two children. During sessions restraints used to manage subjects were removed. After a baseline measure, required practice of repeated vertical arm movements was made contingent upon each response. Later, this procedure was combined with reinforcement under a differential reinforcement of other behavior schedule. Arm exercise alone produced a substantial decrease in head-hitting, while the combination treatment engendered near-zero levels. Subsequently, reduction of head-hitting was extended to several contexts by regular ward staff. This type of treatment appears as effective with self-injurious behavior as it is with stereotyped behavior.

Arm↗

PubMed1981

Behavioral changes in mice following benzene inhalation.

Although benzene is an important occupational health hazard and a carcinogen, the possibility that behavioral changes may forewarn of the later-occurring hematological changes has not been investigated. A time-sampling protocol was used to quantify the occurrence of 7 categories of behavior in the homecage following daily 6-hr exposures to two strains of adult mice (CD1 and C57BL/6J). The behavioral categories were stereotypic behavior, sleeping, resting, eating, grooming, locomotion, and fighting. The inhalation exposures were designed to reflect occupational exposure. Dynamic vapor exposure techniques in standard inhalation chambers were employed. Exposure to 300 or 900 ppm benzene increased the occurrence of eating and grooming and reduced the number of mice that were sleeping or resting. The responses to benzene of both the CD1 and the C57 strains were similar. The positive findings with benzene inhalation indicate the utility of behavioral investigations into the toxicology of inhaled organic solvents. The methods described herein illustrate an objective observation of animal behavior that is capable of documenting toxicity and of guiding detailed follow-up studies aimed at mechanism of action.

Animals↗

PubMedDate not supplied

[Evaluation of psychological characteristics in the preoperative phase of patients with mental retardation].

OBJECTIVES: To make easier the psychological evaluation of patients affected by Mental Retardation and scheduled for general anesthesia. DESIGN: A form prepared by the Psychological Service of the IRCCS "Oasi Maria SS" in collaboration with the Service of Anesthesia was evaluated prospectively. The form is addressed to relatives and psychologists; the interviewed person is firstly asked for a short description of patient's personality and for any suggestion useful to patient's management; secondly it is requested to assign a score from 1 (never present) to 5 (always present) to 44 items concerning adaptive capacities (divided into body scheme, spoken language, receptive language, mimic-gestural language, temporal orientation, memory), emotional and social fields (including sensibility, dependence, and social behaviors), problematic and stereotyped behaviors. SETTING: A medical and psychological Institute aimed at the study of Mental Retardation. PATIENTS: Twenty-five patients affected by Mental Retardation and scheduled for general and dental surgery. RESULTS: The form supplied a great deal of information and suggestions for patient management. Subjects that did not cooperative with the anesthetist presented lower scores about the ability to use mimic-gestural language (p < 0.05) and higher scores about the presence of anxiety or fear caused by the sight of syringes or blood (p < 0.05) and about behaviors of flight, isolation, or aggression caused by fear (p < 0.05). By contrast, patients presenting mild or moderate degrees of Mental Retardation differentiated from patients with serious degree of Mental Retardation about body scheme (p < 0.001), spoken language (p < 0.05), receptive language (p < 0.001), temporal orientation (p < 0.001) and memory (p < 0.001). CONCLUSIONS: The form was very useful to plan patient management. These data suggest that the lack of cooperation by some patients affected by Mental Retardation is related to fear, anxiety, and incapacity to communicate rather than to the degree of Mental Retardation.

Adolescent↗

PubMed1990

Central catecholaminergic dysfunction and behavioural disorders following hypoxia in adult rats.

Wistar male rats, 3-4 months old, were made to breathe for 6 h a sub-lethal hypoxic atmosphere consisting of 8% oxygen and 92% nitrogen. Following this treatment, these rats were subjected to a series of behavioral and biochemical tests starting 30 days and ending at about 180 days after the hypoxic insult. an age-matched control group was subjected to the same series of tests. The following findings were made at the time interval indicated, relative to controls: (1) At 30-35 days, diurnal (3 h) and nocturnal (12 h) locomotor activities decreased by about 25%. (2) At 40-45 days, amphetamine in the dose range of 0.25-1 mg/kg proved less effective in eliciting an increase in motor activity and stereotypic behavior. (3) At about 50 days, apomorphine in the dose range 0.25-0.5 mg/kg caused an increase in stereotypic behavior. (4) At 60-65 days, alpha-methyl-p-tyrosine at the dose of 50 mg/kg caused a more pronounced hypoactive syndrome and a slower rate of recovery of motor activity. (5) At 75-90 days, performance in the active avoidance test was inferior to that of controls. (6) At 180 days, and one hour after a dose of 200 mg/kg alpha-methyl-p-tyrosine, the turnover rates of hippocampal norepinephrine and caudate-putamen dopamine were much below control. One may tentatively conclude that one of the effects of hypoxia in adult rats is a lesion producing long-term behavioral disorders which are partly ascribed to dopaminergic and, possibly noradrenergic, dysfunction.

Age Factors↗

PubMed1979

Metabolism correlates of cocaine-induced stereotypy in rats.

An increase in stereotyped behavior was observed in rats injected daily with cocaine (40 mg/kg, IP), as compared with the first day. This increase persisted 14 days after discontinuation of the drug treatment, and corresponded to increased levels of 3H-cocaine norcocaine and benzoylecgonine in brain. Pretreatment of the animals with SKF-522A, an inhibitor of cocaine demethylation, produced a decrease in stereotypy rating and concomitantly a lower level of 3H-norcocaine in the brain. The role of this metabolite in the production of cocaine-induced stereotyped behavior is discussed.

Animals↗

PubMed2002

Gamma-vinyl GABA, an irreversible inhibitor of GABA transaminase, alters the acquisition and expression of cocaine-induced sensitization in male rats.

We examined the effect of (+/-)-gamma-vinyl GABA (GVG, Vigabatrin), an irreversible inhibitor of the enzyme GABA transaminase, on the acquisition and expression of cocaine-induced sensitization in albino male Sprague-Dawley rats. Animals received a single injection of 1 ml/kg i.p. of 0.9% saline or 15 mg/kg i.p. of (-)-cocaine and locomotor activity was assessed using automated locomotor cages and stereotyped behaviors were scored using a 4-point rating scale (Day 1). Subsequently, animals were given 15 mg/kg i.p. of cocaine every 48 h in their home cage for 1 week (Days 3, 5, and 7) and then given no treatment for 1 week. A challenge injection of 15 mg/kg i.p. of cocaine, but not vehicle, produced a significant increase in locomotor activity and stereotyped behaviors on Day 15 compared to animals that received cocaine on Day 1. Administration of 75 mg/kg i.p. of GVG 2.5 h before the cocaine injections did not significantly alter the acquisition of cocaine-induced locomotor sensitization. However, 150 mg/kg i.p. of GVG significantly attenuated the acquisition of cocaine-induced locomotor sensitization. Administration of 150 mg/kg i.p. of GVG 2.5 h before the cocaine challenge injection on Day 15 significantly attenuated the expression of cocaine-induced locomotor sensitization. Acquisition and expression of cocaine-induced sensitization of stereotypy was also significantly attenuated by 150 mg/kg i.p. of GVG. Since sensitization may be one of the factors involved in relapse to drug use, the present results, in combination with previous findings that GVG blocks the rewarding and incentive motivating effects of cocaine, suggest that GVG might prove useful in the treatment of cocaine addiction.

4-Aminobutyrate Transaminase↗