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PubMed1986

[Treatment of compulsive eating disorders in an autistic girl by combining behavior therapy and pharmacotherapy. Case report].

A young adolescent girl (13.5 years old) with a compulsive eating disorder and gross obesity was treated with a combination of behavior therapy and fenfluramine (Ponderax). The behavior modification program used was adapted from Reiss's program, an approach that had proven effective in individuals with hyperphagia and overweight who had no additional emotional problems or brain damage. In our patient the problem was complicated by the presence of autism, with compulsive eating being particularly ingrained as a form of stereotyped behavior. We therefore decided to administer fenfluramine concurrently because it is known to have both an appetite-depressing effect and a positive effect on behavioral disturbances characteristic of autistic individuals. During inpatient treatment the girl lost weight and showed changes in behavior. The changed eating behavior was still being maintained many months after discharge and after fenfluramine had been discontinued. We assume that drug treatment provided an important kind of support for the behavioral treatment program. Further, we attribute the emotional stabilization in this autistic girl to fenfluramine. We now plan to extend this treatment approach to other subjects with similar problems.

Adolescent↗
PubMed1993

Recent developments in alcoholism:typologies in women.

Historically, there has been considerable interest in developing alcoholic typologies with the belief that typologies would facilitate treatment development and stimulate meaningful research. Most of the existing typologies can be classified into one of two broad camps: the behavioral typologies and the family history/genetic typologies. Recent work has focused on the integration of these two strategies into comprehensive typological systems. This chapter provides an overview of the major typologies, noting their various strengths and weaknesses. Common weaknesses among existing typologies are that female alcoholics have not been adequately studied and/or are stereotyped. Behavioral heterogeneity within the female alcoholic population is discussed and suggestions for typological development are noted.

Alcoholism↗
PubMed1986

Behavioral and neurotransmitter changes in the urease-infused rat: a model of congenital hyperammonemia.

Rats implanted with subcutaneous or intraperitoneal osmotic minipumps infusing 0.8-1.25 IU urease/kg/h develop sustained hyperammonemia (range 137-497 microM, controls 88 +/- 51 microM +/- SD) for 5-7 days. Glutamine levels are also significantly elevated in plasma (677 +/- 166 versus 428 +/- 122 microM) and cerebral cortex (13.2 +/- 9.8 versus 4.7 +/- 2.8 nmol/mg tissue). Neurobehavioral abnormalities include decreased food intake and increased stereotypic activity. Increased serotonin turnover was suggested by elevated levels of tryptophan and 5-hydroxyindoleacetic acid in cerebral cortex, brain stem, and cerebellum of urease-infused compared to sham-operated animals. There were no changes in norepinephrine or gamma aminobutyric acid, and there was no correlation between the degree of hyperammonemia or glutaminemia and brain levels of tryptophan or biogenic amines. Animals receiving a tryptophan-deficient diet had significantly lower levels of tryptophan and 5-hydroxyindoleacetic acid in brain regions compared to animals receiving a normal tryptophan intake, under both control and hyperammonemic conditions. Despite the prevention of increased serotonin flux in hyperammonemic animals receiving a tryptophan-deficient diet, food intake and weight declined and there was increased stereotypic behavior.

Ammonia↗
PubMed1977

Open-field behavior after intravenous amphetamine analogues in rats.

A variety of behaviors were studied in an open-field setting after i.v. amphetamine (0.5, 2.0, 8.0 mg/kg), phenmetrazine (1.0, 4.0, 16.0 mg/kg), or fenfluramine (1.0, 4.0, 16.0 mg/kg). Amphetamine and phenmetrazine increased ambulation initially and rearing during the whole experiment, and decreased grooming. At 30 and 60 min, with the three higher doses of amphetamine, stereotyped behaviors interfered with and decreased both ambulation and groomin. Fenfluramine decreased ambulation, rearing, and grooming, and was the only drug to induce backing. The technique seems to be a simple and rapid method to establish dependence liability in amphetamine analogues. Interrater and test-retest reliability was established through ITV recordings.

Animals↗
PubMed2005

The effects of neurochemical lesioning of dopaminergic terminals in early ontogenesis on behavior in adult rats.

6-Hydroxydopamine, which induces selective degeneration of the dopaminergic system of the brain, was given intraamniotically to rats on days 13 and 17 of intrauterine development at a dose of 75 microg/fetus. Similar experiments were performed with 6-hydroxydopamine on days 4 and 10 of neonatal life. Rats were subsequently reared and motor and emotional (dopamine-dependent) types of behavior were studied in adulthood, addressing behavior in the open field test, rotatory behavior, anxiety in an elevated cross maze, a place-preference conditioned response, acquisition of the ability to differentiate new and old arms in a Y maze, aggressivity in the "foreigner-resident" test, and self-stimulation in a Skinner box. Prenatal exposure, to a lesser extent than postnatal exposure, initiated rotatory and stereotypical behavior, decreased the level of anxiety (fear) in the elevated maze, and reinforced the effects of phenamine in the conditioned place-preference test, impaired the differentiation of old and new Y-maze arms, impaired aggressivity in the "foreigner-resident" test, and impaired self-stimulation of the lateral hypothalamus. It is concluded that the early postnatal period of development is more sensitive to the action of this neurotoxin than the prenatal period. This is associated with the critical periods of the formation of the dopaminergic system during ontogenesis, which depend on synaptogenesis.

Age Factors↗
PubMed1997

Sequential arousal and airway-defensive behavior of infants in asphyxial sleep environments.

Infants are prone to accidental asphyxiation. Therefore, we studied airway-defensive behaviors and their relationship to spontaneous arousal behavior in 41 healthy sleeping infants (2-26 wk old), using two protocols: 1) infant was rebreathing expired air, face covered by bedding material; and 2) infant was exposed to hypercarbia, face uncovered. Multiple measurements of respiratory and motor activities were recorded (video, polygraph). The infants' response to increasing hypercarbia consisted of four highly stereotyped behaviors: sighs (augmented breaths), startles, thrashing limb movements, and full arousal (eyes open, cry). These behaviors occurred abruptly in self-limited clusters of activity and always in the same sequence: first a sigh coupled with a startle, then thrashing, then full arousal. Incomplete sequences (initial behaviors only) occurred far more frequently than the complete sequence and were variably effective in removing the bedding covering the airway. In both protocols, as inspired CO2 increased, incomplete arousal sequences recurred periodically and with increasing frequency and complexity until the infant either succeeded in clearing his/her airway or was completely aroused. Spontaneous arousal sequences, identical to those occurring during hypercarbia, occurred periodically during sleep. This observation suggests that the infant's airway-defensive responses to hypercarbia consist of an increase in the frequency and complexity of an endogenously regulated, periodically occurring sequence of arousal behaviors.

Arousal↗
PubMed1988

Bizarre behavior following the ingestion of levo-desoxyephedrine.

This is the first reported case of transvestism in a heterosexual male that occurred only after ingestion of the contents of six to eight Vicks inhalers. The patient's gender cross-dressing was associated with sexual excitement and masturbatory behavior. This case is consistent with other cases of gender cross-dressing and sexual excitement following inhaler abuse, but in the previous cases reported the subjects were homosexual men. Levo-desoxyephedrine, also known as levo-methamphetamine, the main active ingredient in Vicks Inhalers, is known to have amphetamine-like properties. Stereotypic behavior is consistent with behavior that follows the use of amphetamine. Transvestism has traditionally been thought to be based on a psychodynamic model; however, the authors postulate several biochemical mechanisms whereby levo-desoxyephedrine may play a role in the bizarre behavior exhibited by this 32-year-old man. It is suggested that inhalers be placed in a new class of drugs that can be dispensed only by a pharmacist or physician.

Adult↗
PubMed1994

MK-801 does not prevent acute stimulatory effects of amphetamine or cocaine on locomotor activity or extracellular dopamine levels in rat nucleus accumbens.

Recent work has shown that the development of behavioral sensitization to cocaine, amphetamine, and morphine is prevented by coadministration of N-methyl-D-aspartate (NMDA) antagonists such as MK-801. This suggests that NMDA receptors mediate long-term changes in neuronal responsiveness essential for the development of behavioral sensitization, similar to their role in other forms of neuronal plasticity. However, other studies, suggesting that NMDA receptor antagonists interfere with acute behavioral effects of psychomotor stimulants, call this interpretation into question and suggest that the ability of NMDA antagonists to prevent sensitization may reflect blockade of the acute effects of psychomotor stimulants. To examine this issue, behavioral and microdialysis studies assessed the effect of pretreatment with 0.1 mg/kg MK-801 on the ability of amphetamine and cocaine to stimulate locomotor activity and elevate extracellular dopamine (DA) levels in nucleus accumbens; this dose of MK-801 prevents sensitization when coadministered repeatedly with these stimulants. MK-801 pretreatment enhanced amphetamine-stimulated horizontal locomotion and stereotyped behavior. MK-801 pretreatment produced a modest attenuation of cocaine-stimulated horizontal locomotion, which may have reflected enhancement by MK-801 of certain components of cocaine-stimulated stereotypy. There was no effect of MK-801 pretreatment on the ability of amphetamine or cocaine to elevate extracellular DA levels in nucleus accumbens. These results suggest that the acute effects of cocaine and amphetamine on locomotor activity and extracellular DA levels are not prevented by MK-801, and that MK-801 must act through other mechanisms to prevent the development of behavioral sensitization.

Amphetamine↗
PubMed1995

Effects of flumazenil on ethanol withdrawal syndrome in rats.

Effects of flumazenil (Ro 15-1788, CAS 78755-81-4) on ethanol withdrawal syndrome (EWS) has been investigated in rats. Behavioral EWS symptoms appeared during the first 6 h of ethanol withdrawal. Flumazenil (2.5 and 10 mg/kg i.p.) increased horizontal and vertical locomotor activity significantly and also precipitated abnormal gait and agitation at the beginning of EWS in a dose dependent manner. However, thereafter it reduced the severity of abnormal posture and gait, tail stiffness, agitation and stereotyped behavior in a dose dependent manner. At the 6th hour of EWS, flumazenil (10 mg/kg) reduced total EWS score significantly, but shortened the latency of audiogenic seizures and increased the severity of wet dog shakes. Flumazenil (2.5 and 10 mg/kg) did not elicit behavioral EWS symptoms and audiogenic seizures in non-dependent (control) rats. It did not cause any significant change on locomotor activities in these groups. According to those results, certain actions of flumazenil on the experimental EWS may suggest a potential beneficial effect of this drug in the treatment of EWS in alcoholics, but its enhancing effects on some behavioral EWS symptoms and a potential proconvulsant activity may be a drawback for its use in the treatment of EWS.

Alcohol Drinking↗
PubMed1995

Effects of subchronic treatments with SM-9018, a novel 5-HT2 and D2 antagonist, on dopamine and 5-HT receptors in rats.

1. Receptor binding and behavioral studies were performed to compare the effects of subchronic treatments with SM-9018, a novel 5-HT2 and D2 antagonist, and with haloperidol (HAL) on dopamine and 5-HT receptors in rats. 2. SM-9018 treatment (10 mg/kg/day p.o.) for 2 weeks did not significantly change the density (Bmax) of striatal D2 receptors or the incidence of stereotyped behavior induced by apomorphine (APO). By contrast, HAL treatment (3 mg/kg/day p.o., for 2 weeks) significantly increased the D2 receptor density by about 55% and markedly enhanced the behavioral response to APO. 3. The density of 5-HT2 receptors in the cerebral cortex was significantly reduced (about 20%) by SM-9018 treatment without being affected by HAL. However, the hyperthermic response of rats to p-chloroamphetamine (p-CAMP, a putative 5-HT releaser) was unaltered by either treatment. 4. Neither SM-9018 nor HAL treatment changed the density of 5-HT1A receptors in the hippocampus. 5. These findings suggest that SM-9018 is weaker than HAL in inducing up-regulation and supersensitivity of the striatal D2 receptors after the subchronic treatment.

Animals↗
PubMed1996

Distinct grooming patterns induced by intracerebroventricular injection of CRH, TRH and LHRH in male rats.

This paper reports the effects on grooming, related behaviors and levels of anxiety induced by the hypophysiotropic peptides corticotropin-releasing hormone (CRH, 1 microgram, 0.2 nmol, icv), thyrotropin-releasing hormone (TRH, 100 micrograms, 275 nmol, icv) and luteinizing hormone-releasing hormone (LHRH, 1.5 micrograms, 1.3 nmol, icv) administered into the lateral ventricle of the brain (icv) of adult male rats of a Holtzman-derived colony (N = 15, each group). CRH induced an increase in total grooming scores, whereas LHRH, TRH and vehicle had no effect. CRH strongly increased face and head grooming and induced head shakes. The time spent in rearing and gnawing was significantly decreased. In the plus-maze, CRH reduced the time of exploration in the open arm. TRH increased face grooming and induced body shakes. LHRH had no effect on grooming or rearing behavior. No body or head shakes were observed after LHRH administration. Scoring of individual grooming elements demonstrated differences in action of the three peptides. Although both CRH and TRH increased face grooming, only CRH induced head grooming. Furthermore, CRH induced predominantly head shakes while TRH increased body shake activity. In contrast, CRH was anxiogenic and TRH appeared to induce stereotyped behavior. From the characterization of grooming elements and related responses, we conclude that each hypophysiotropic peptide induces a specific behavioral pattern.

Analysis of Variance↗
PubMedDate not supplied

[Effect of haloperidol on development of amnesia in aggressive and submissive mice].

The effect of haloperidol on the passive avoidance habit retrieval upon amnesia was studied in C57BL/6J mice with aggressive and submissive behavioral stereotypes formed under agonist confrontation conditions. In the control (untreated) group, the efficacy of the amnesic action of detention in the dangerous compartment on the learning day was reduced for the aggressive stereotype as compared to the submissive one. In the aggressive mice, the administration of haloperidol (0.5 mg/kg) one hour before learning deteriorated the conditional reaction retrieval between 2nd and 13th days of test. In the submissive mice, the administration of haloperidol produced a prolonged antiamnesic effect. Thus, the effect of haloperidol on the violated memory trace reproduction depends on the individual behavioral state.

Aggression↗
PubMedDate not supplied

[Genetic studies in communication disorders].

OBJECTIVES: To review current literature on population, cytogenetic and molecular studies of specific language disorders (SLD) and pervasive developmental disorders (PDD). DEVELOPMENT: Clinical concordance studies in twins and in vertical familial groups suggest polygenic multifactorial modes of inheritance, but in some families an autosomal dominant model may be present. The data favour not a modular, but rather a molar model of the relationship between genes and neural abilities for communicative behaviors. Several extensive genome screenings have demonstrated linkage to specific markers on 7q for SLD, and on 7q and 2q for PDD. The strong evidence of linkage on 7q for both disorders has led to the hypothesis that this region contains several separate quantitative trait loci (QTL) related to different communicative abilities. Mutations in different QTL would facilitate the different disabilities and stereotyped behaviors associated with the phenotypic spectrum of PDD. There are other candidate regions for QTLs but the linkage is weaker and there is little agreement between studies; due, in part, to over extensive inclusion criteria and small sizes of familial groups. CONCLUSIONS: To enhance linkage research in further molecular genetic studies, clinicians must refine behavioral target traits when selecting familial groups and enlarge the size of familial groups by including non handicapped members with related behavioral traits. At present, a chromosome region in 7q shows the strongest evidence for communication related QTL, but other QTL need to be identified elsewhere in the genome in order to explain the genetic contribution to the large spectrum of language and autistic disorders.

Autistic Disorder↗
PubMedDate not supplied

Psychotropic effects of angiotensin II N-terminal fragments: Asp-Arg-Val-Tyr-Ile-His and Arg-Val-Tyr-Ile-His in rats.

In this study the effects of angiotensin II (AII) angiotensin II hexapeptide [AII(1-6)] and angiotensin II pentapeptide [AII(2-6)] on the motility, stereotypy, learning of conditioned avoidance responses (CARs) and recall of a passive behavior making it possible to avoid aversive stimulation in rats, were compared. All the peptides were injected into the lateral cerebral ventricle (icv) in a dose of 1 nmol. AII caused a statistically significant increase in the number of crossings, rearings, and bar approaches in an open field whereas [AII(1-6)] and [AII(2-6)] were inactive in this test. The stereotypic behavior induced by an intraperitoneal (ip) injection of apomorphine (1 mg/kg) and amphetamine (7.5 mg/kg) was statistically significantly enhanced only in the rats which received AII icv. The application of AII, but not that of [AII(1-6)] and [AII(2-6)] resulted in a quicker acquisition of the CARs. A better recall of passive avoidance was achieved only by AII, while the fragments [AII(1-6)] and [AII(2-6)] had no effect. These findings indicate that the 1-6 and 2-6 fragments of AII do not possess a psychotropic activity like that of the parent octapeptide.

Amino Acid Sequence↗
PubMed2002

A shift in information flow between prefrontal cortex and the ventral tegmental area in methamphetamine-sensitized rats.

We examined the effects of long-term methamphetamine (MAP) administration to rats on locomotor traces and reward-seeking behavior that was evaluated through ventral tegmental intracranial self-stimulation (ICSS). Furthermore, using the directed coherence (DCOH) EEG analysis method, correlation of prefrontal cortical and ventral tegmental EEGs was investigated in terms of the direction of information transmission. The results showed a transition from 'mixed type' behavior to 'fixed type' behavior during long-term MAP treatment, accompanied by a gradually diminished rate of ICSS and increased reward threshold. Correlating to these changes, a dominant information flow from ventral tegmental area (VTA) to prefrontal cortex (PFC) was observed after long-term MAP administration. Together with our previously reported finding of reciprocal information flow between PFC and VTA in MAP-induced hyperactive and stereotyped behavior, the present results indicate that information flow and its direction may be useful in explaining the neuronal substrates mediating development of behavioral sensitization. The predominant information flow from the VTA to PFC that occurs with sensitization supports recent speculations concerning impulsivity in drug addiction.

Animals↗
PubMed1996

sigma Receptor antagonists block the development of sensitization to cocaine.

The effects of putative sigma receptor antagonists, BMY-14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine), rimcazole and SR-31742A (cis-3-(hexahydroazepin-1-yl)1-(3-chloro-4- cyclohexylphenyl)propene-1), on the development of behavioral sensitization induced by repeated administration of cocaine were investigated. Acute intraperitoneal injection of 15 mg/kg cocaine in rats induced moderate hyperactivity which mainly consisted of sniffing and rearing. These acute effects of cocaine were hardly affected by co-administration of the sigma receptor antagonists, except that BMY-14802 enhanced, but not significantly cocaine-induced locomotion. While repeated cocaine administration induced a progressive increase in stereotyped behaviors and resulted in sensitization, every sigma receptor antagonists tested attenuated the development of sensitization to cocaine. These prophylactic effects of sigma receptor antagonists against cocaine-induced sensitization were confirmed by the challenge test with cocaine alone after an abstinence. These results were consistent with results of our previous study which revealed that BMY-14802 blocked the sensitization to methamphetamine, another psychostimulant. Therefore, sigma receptors play a crucial role in the development of the psychostimulant-induced sensitization phenomenon, which is a pharmacological model of schizophrenia.

Animals↗
PubMed1987

Prediction of recovery for closed-head-injured adults: an evaluation of the MMPI, the Adaptive Behavior Scale, and a "Quality of Life" Rating Scale.

Twenty-five closed-head-injured adults (24 males, 1 female; M age = 28.8 years) were classified as "recovered" if they had returned to work, school, or a sheltered workshop for which pay was received and "non-recovered" if they did not meet these criteria. Current status was compared with MMPI, Adaptive Behavior Scale (ABS), and "Quality of Life" Rating Scale (QLRS) scores at time of entry into a rehabilitation program. The "non-recovered" group was significantly higher on the PD (Psychopathic deviate) scale. No differences were found between groups on the Sc (Schizophrenia) or K (Validity) scales. The "recovered" group was significantly higher on the ABS Economic Activity domain and significantly lower in the Violent & Destructive, Antisocial, Rebelliousness, Untrustworthiness, Stereotyped Behavior & Odd Mannerisms, and Psychological Disturbance behavior domains. The self-ratings (QLRS) of the "nonrecovered" subjects were significantly more distinct from the ratings made by their relatives or significant others than were those of the "recovered" subjects.

Adult↗
PubMed1995

Changes in the behavioral parameters following the lipopolysaccharide administration in goats.

The present study was aimed at the establishment of an experimental model for the numerical assessment of sick animal behavior. Four goats were given bolus injections of 200 ng/kg of lipopolysaccharide (LPS) or vehicle (0 hr) under non-restrained conditions, and observed for behavioral changes and clinical symptoms during the period between -1 and 10 hr. The apparent clinical symptoms of miosis and shivering were observed during the period from 39.5 +/- 3.1 to 296.5 +/- 9.9 min and from 46.0 +/- 2.3 to 251.0 +/- 15.5 min after the LPS administration, respectively. As to the general behaviors, the total length for standing and sternum lying during the period from 0 to 5 hr after LPS administration showed no change, however, that for feeding and rumination, and the cumulative number of grooming episode were significantly reduced as compared to the control period. On the other hand, the cumulative numbers of urination, defecation and yawning showed a tendency to increase but not significantly. These results suggest that stereotyped behavioral responses, which are typically seen in acute phase of sickness, can be transiently induced in goats by treating them with LPS.

Animals↗