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PubMed1976

Somatostatin and thyrotropin releasing hormone: central effect on sleep and motor system.

The hypothalamic hormones, somatostatin (SRIF or GH-RIH) and thyrotropin releasing hormone (TRH) applied intraventricularly into rat brain had a considerable effect on motor function and resulted in profound alterations in the sleep-waking pattern. While TRH induced primarily an increase in exploratory and motor stereotyped behavior, the effect of somatostatin was striking and prolonged: stereotyped circular running in many instances evolved into catatonia, paraplegia-in extension and/or tonic-clonic seizures.

Animals↗
PubMed2004

Differential dose effects of central CRF and effects of CRF astressin on pig behavior.

The elevation of central corticotropin releasing factor (CRF) causes an increase in behavioral activity, including increases in overall activity and oral/nasal/facial (ONF) chewing-rooting-rubbing behaviors in the pig and similar behaviors in other species. This study detailed changes in the frequency, duration and sequences of behaviors after central administration of vehicle or porcine CRF (pCRF at 0.5, 5.0, 50 and 150 microg). A sequential analysis described the complex behaviors induced in a dose-dependent fashion by central pCRF. The frequency and duration of ONF behaviors were significantly increased among pigs receiving 50 microg of pCRF. For behaviors such as ONF, 50 microg represented a breakpoint at which the frequency and duration of single behaviors increased. Pigs receiving 50 microg of pCRF were considerably more active and exhibited more ONF behaviors than did pigs receiving lower doses. The highly sensitive sequential analysis revealed that very low doses of central pCRF induced subtle changes in sequences of behaviors. Low doses of central pCRF (0.5 microg) induced fear-related behavioral sequences that included ONF behaviors alternating with periods of inactivity. Central injection of astressin, a CRF receptor antagonist, blocked many, but not all, of CRF-induced behaviors. Compared with saline-injected control pigs, central pCRF increased general activity, ONF, fear-related freezing and sham chewing behaviors. When pCRF was given following astressin, fear-related freezing behaviors were not different compared with pigs receiving saline. However, pigs given astressin plus pCRF showed elevated sham chewing compared with saline-injected control pigs, as did pigs receiving intracerebroventricular (ICV) pCRF. These data indicate that central pCRF activates brain mechanisms associated with hyperactivity, ONF and fear-related behaviors, whereas other behaviors induced by pCRF may be nonspecifically mediated by CRF. Astressin antagonized some, but not all, pCRF-induced behaviors. This model represents the induction of hyperactivity and stereotyped behaviors, which may represent a new model for the study of mania or obsessive-compulsive behaviors.

Animals↗
PubMed2006

Behavioral electrophysiology of psychostimulants.

The motor-activating effects of amphetamine and other psychostimulants such as cocaine depend on an increase in dopamine (DA) transmission in the striatum, a key component of the basal ganglia and the forebrain motive circuit. This review focuses on research aimed at using electrophysiological techniques--including extracellular unit recording and iontophoresis--in alert, fully functioning animals to understand how these drugs alter striatal neuronal processing under behaviorally relevant conditions. The data indicate that DA works in conjunction with glutamate (GLU), an excitatory amino acid, to enhance the signal-to-noise ratio of afferent information. This DA-GLU interaction appears to play a critical role in the amphetamine-induced activation of striatal neurons. The pattern of striatal activation, moreover, changes as the behavioral response changes from unfocused locomotion to highly focused, stereotyped behavior, but interestingly, the striatal response pattern is not reflected in substantia nigra reticulata, a primary target of striatal efferents. Although cocaine also activates striatal neurons during behavior, the underlying mechanisms appear to be complicated by factors unique to this drug and deserve further evaluation. Collectively, these findings provide unique insight into the neuronal processes by which the striatum participates in psychostimulant-induced motor behavior.

Animals↗
PubMed1997

A study of cognitive development and behavior problems in mentally retarded children.

Cognitive development in seventy-one mentally retarded children (19 autistic, 52 non-autistic; aged 7-19 years) from a school for handicapped children was studied, using Ohta's scale for evaluating cognitive development level based on language comprehension (Ohta's stage), and other developmental scales. Behavior problems were also examined. The present study reports on the utility of Ohta's stage in non-autistic children, and the relationship between cognitive development level and behavior problems in mentally retarded children. In non-autistic children, there were temporal correlations between Ohta's stage and other development scales (a standard developmental test, speech development, symbolic play development, imitation development), suggesting that in non-autistic children as well, Ohta's stage may serve well as a scale for cognitive development, and reflect symbolic representational functioning. In non-autistic children, most behavior problems in feeding, elimination and sleeping, hyperkinesis, hypokinesis, stereotyped behaviors, self-injurious behavior and licking were closely associated with cognitive development level, and were more often noted in children of lower cognitive development level rather than only in the severely mentally retarded children. Some behavior problems may often occur in the sensorimotor period and hardly occur in the symbolic representational period.

Adolescent↗
PubMed1982

Mechanisms of dopamine antagonism by morphine in rodents.

A number of investigators have concluded on the basis of a substantial and compelling body of biochemical, pharmacological and behavioral evidence, that opiates and particularly morphine, directly block central dopamine (DA) receptors. This evidence includes the recent finding that cataleptogenic doses of morphine suppress 3H-spiroperidol binding to striatal membranes ex vivo. On the other hand, an important albeit relatively sparse literature of experimental evidence exists suggesting that morphine and other mu-receptor opiates do not directly bind to central dopaminergic receptors. The most convincing evidence to this effect are behavioral findings that morphine potentiates rather than inhibits the stereotyped behavior induced by the direct DA agonist apomorphine and biochemical evidence demonstrating a failure of 3H-morphine or 3H-dihydromorphine to specifically bind central DA receptors in striatal tissue. (Indeed, even those reports that demonstrated a morphine induced suppression of 3H-spirioperidol labelling of DA receptors failed to find a direct effect on post-synaptic receptors.) Evidence is presented in this report to show that morphine acts presynaptically to acutely inhibit DA release, and thus, that morphine inhibition of DA receptor mediated responses is indirect, being the result of an inhibition of pre-synaptic DA release rather than a direct effect exerted on post-synaptic DA receptors themselves.

Animals↗
PubMed1977

Behaviors observed during S- in a simple discrimination learning task.

Key pecking of pigeons was reinforced with food in the presence of a horizontal line and never reinforced in the presence of a vertical line. Highly stereotyped behaviors, as well as key pecking, were observed and recorded in the presence of both stimuli. Results showed that a high proportion of time spent in the presence of the horizontal line was occupied by key pecking, a high proportion of time in the presence of the vertical line was occupied by stereotyped nonkey-pecking behaviors, and intermediate proportions of time spent in the presence of intermediate stimuli were occupied by each class of behavior during generalization tests. Similar running rates (number of key pecks divided by observed key-pecking time) were obtained in the presence of all stimuli, indicating that changes in time rather than tempo accounted for the changes in overall rates of key pecking. An exception occurred in responding to the horizontal line as differential performance was developing. In addition to an increase in time spent key pecking, increased running rates occurred in seven of eight birds, suggesting that both time allocation and tempo play a role in behavioral contrast of overall rates of key pecking.

Journal Article↗
PubMed1989

Enhanced behavioral stereotypies elicited by intrastriatal injection D1 and D2 dopamine agonists in intact rats.

Five components of behavior elicited by dopamine (DA) agonists (locomotor hyperactivity, sniffing, oral activity, grooming and paw nibbling) were evaluated after bilateral infusion of the selective D1 agonist fenoldopam (SKF 82526; 2.5-10 micrograms), the selective D2 agonist quinpirole (LY 171555; 5-40 micrograms) and the muscarinic cholinergic antagonist scopolamine (5-20 micrograms) into the ventral striatum of awake, unrestrained rats. Simultaneous bilateral infusion of various dose combinations of fenoldopam (2.5-10 micrograms) and quinpirole (5-20 micrograms) elicited dramatic increases in stereotyped behaviors relative to the effects produced by corresponding doses of each drug alone. Stereotyped sniffing and paw nibbling (self-directed oral activity) were markedly enhanced, whereas conventional oral behaviors (licking, chewing and/or biting) were either slightly or not at all increased. These potentiated responses were reduced or blocked by concomitant infusion of either the selective D1 antagonist SCH 23390 (1 and 5 micrograms) or the selective D2 antagonist sulpiride (0.15 microgram). Scopolamine (10 micrograms) only slightly increased the effects of quinpirole (5 micrograms) on both sniffing and oral behaviors, whereas it dramatically potentiated the effects of fenoldopam (2.5 micrograms) on oral activity; sniffing was only slightly increased. The effects of both drug combinations were almost completely antagonized by infusion of either SCH 23390 (1 microgram) or sulpiride (0.1 microgram). The results demonstrate that the synergistic effects of co-activation of D1 and D2 receptors observed after systemic administration are mediated at least in part by an interaction at the level of the striatum. Differences and similarities between the behaviors expressed after various treatments are discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2002

Excitotoxic lesions of the pedunculopontine differentially mediate morphine- and d-amphetamine-evoked striatal dopamine efflux and behaviors.

Cholinergic and glutamatergic cells in the pedunculopontine tegmental nucleus are a principal source of excitatory input to midbrain dopamine neurons projecting to the striatum. Disruption of these brainstem inputs has been shown to respectively enhance and reduce psychostimulant and opiate self-administration in rats. In the present study, d-amphetamine- and morphine-induced behaviors and dorsal striatal dopamine efflux, measured using in vivo chronoamperometry, were investigated 21 days after bilateral excitotoxic (ibotenate) lesions of the pedunculopontine in rats. Compared to sham-operated controls, pedunculopontine lesions enhanced stereotyped behaviors induced by a challenge injection of d-amphetamine (1.5 mg/kg, i.p.) to an extent that markedly interfered with the expression of locomotor behavior. A significant augmentation in striatal dopamine efflux was also observed in these lesioned animals under urethane anesthesia in response to a similar challenge injection of d-amphetamine (1.5 mg/kg, i.v.) 2 days following these behavioral observations. In direct contrast, pedunculopontine lesions in a separate group of rats significantly attenuated morphine-induced (2 mg/kg, i.p.) stereotyped activity, although no significant differences were observed in locomotion compared to sham-operated animals. Under urethane anesthesia, these lesions attenuated striatal dopamine efflux evoked by a similar challenge injection of morphine (2 mg/kg, i.v.). These findings indicate that the pedunculopontine differentially mediates the pharmacological actions of two diverse drugs of abuse on striatal dopamine neurotransmission and resultant behaviors. These results also imply that the pedunculopontine tegmental nucleus may serve as a major striatal-motor interface in the processing of salient environmental stimuli, and their incentive rewarding impact on dopamine-mediated behavioral responses.

Animals↗
PubMed1978

Body build stereotypes and self-identification in three age groups of females.

Body build stereotypes of three age groups (6, 15, and 19 years old) of average weight and "heavy" female students were studied. First, the students were asked to circle one adjective from each of 28 antonym pairs, which was "most like" themselves. Concurrently, side-view figures of a female endormorph, an ectomorph, and a mesomorph were shown to each student. The figures were of the approximate age of the student. She was asked to point to one of the figures which "best fit" the adjectives in each of the 18 antonym pairs as they were read aloud. Lastly, each student was asked to choose one of the figures which "most looked" like themselves and the one which they would most want to "look like". Thus, discrepancies could be detected between one's self description and one's description of others with a very similar physique. The hypothesis that females would have similar physique preferences and aversions as those of males in a previous study (3) was confirmed. Females preferred the mesomorph figure (p less than .001) and at least favored the endomorph figure (p less than .001). The ectomorph figure was viewed less negatively than the endomorph figure (p less than .01). The youngest group showed more preference towards the endomorph and ectomorph figures then did the two older groups. "Heavy" physique students rejected the behavioral stereotypes descriptive of themselves even though they earlier had associated the very same stereotypes to the physique most like their own.

Adolescent↗
PubMedDate not supplied

Prenatal exposure to dichlorvos: physical and behavioral effects on rat offspring.

The effects of prenatal exposure to dichlorvos (DDVP), an organophosphate (OP) pesticide, on pups' physical and neurobehavioral developments were investigated. Forty pregnant rats were treated by gavage with 8.0 mg/kg DDVP or its vehicle (1 ml/kg) from the 6th to the 15th day of pregnancy. At birth, pups were weighed, the litters culled to eight animals (four male and four female), and then observed for physical (pinna detachment, incisor eruption, eye opening, testes descent, and vaginal opening) and neurobehavioral developments (palmar grasp, surface righting, negative geotaxis, and open-field behaviors). As adults, open-field, apomorphine-induced stereotypy, and passive avoidance behaviors were also assessed. Results showed no differences between the body weight of DDVP and control-treated groups. No differences were observed on the measures of physical and neurobehavioral development. Locomotor activity of male pups at 21 days of age was decreased by DDVP exposure. Adult experimental offspring showed a decreased locomotor frequency and an increased immobility duration on open-field behavior in relation to control animals; the apomorphine-induced stereotyped behavior was decreased by the pesticide exposure as well as performance on the passive avoidance task. These data suggest that prenatal DDVP exposure was able to decrease offspring motor function (adolescence and adults) and conditioned response learning, probably by interference with the cholinergic-dopaminergic balance of activity involved with the control of motor function as well as the cholinergic system that modulates learning process.

Analysis of Variance↗
PubMed2006

Blueprints for behavior: genetic specification of neural circuitry for innate behaviors.

Innate behaviors offer a unique opportunity to use genetic analysis to dissect and characterize the neural substrates of complex behavioral programs. Courtship in Drosophila involves a complex series of stereotyped behaviors that include numerous exchanges of multimodal sensory information over time. As we will discuss in this review, recent work has demonstrated that male-specific expression of Fruitless transcription factors (Fru(M) proteins) is necessary and sufficient to confer the potential for male courtship behaviors. Fru(M) factors program neurons of the male central and peripheral nervous systems whose function is dedicated to sexual behaviors. This circuitry seems to integrate sensory information to define behavioral states and regulate conserved neural elements for sex-specific behavioral output. The principles that govern the circuitry specified by Fru(M) expression might also operate in subcortical networks that govern innate behaviors in mammals.

Animals↗
PubMed2000

Behavioral responses to cocaine and amphetamine administration in mice lacking the dopamine D1 receptor.

Cocaine and amphetamine can induce both short-term and long-term behavioral changes in rodents. The major target for these psychostimulants is thought to be the brain dopamine system. To determine whether the dopamine D1 receptor plays a crucial role in the behavioral effects of psychostimulants, we tested both the locomotor and stereotyped behaviors in D1 receptor mutant and wild-type control mice after cocaine and amphetamine treatments. We found that the overall locomotor responses of D1 receptor mutant mice to repeated cocaine administration were significantly reduced compared to those of the wild-type mice and the responses of the D1 receptor mutant mice to cocaine injections were never significantly higher than their responses to saline injections. D1 receptor mutant mice were less sensitive than the wild-type mice to acute amphetamine stimulation over a dose range even though they exhibited apparently similar behavioral responses as those of the wild-type mice after repeated amphetamine administration at the 5 mg/kg dose. Immunostaining experiments indicated that there was no detectable neurotoxicity in the nucleus accumbens in both D1 receptor mutant and wild-type mice after repeated amphetamine administration. The data suggest that the D1 receptor plays an essential role in mediating cocaine-induced behavioral changes in mice. Moreover, the D1 receptor also participates in behavioral responses induced by amphetamine administration.

Amphetamine↗
PubMed2005

Cytogenetic abnormalities and fragile-X syndrome in Autism Spectrum Disorder.

BACKGROUND: Autism is a behavioral disorder with impaired social interaction, communication, and repetitive and stereotypic behaviors. About 5-10 % of individuals with autism have 'secondary' autism in which an environmental agent, chromosome abnormality, or single gene disorder can be identified. Ninety percent have idiopathic autism and a major gene has not yet been identified. We have assessed the incidence of chromosome abnormalities and Fragile X syndrome in a population of autistic patients referred to our laboratory. METHODS: Data was analyzed from 433 patients with autistic traits tested using chromosome analysis and/or fluorescence in situ hybridization (FISH) and/or molecular testing for fragile X syndrome by Southern and PCR methods. RESULTS: The median age was 4 years. Sex ratio was 4.5 males to 1 female [354:79]. A chromosome (cs) abnormality was found in 14/421 [3.33 %] cases. The aberrations were: 4/14 [28%] supernumerary markers; 4/14 [28%] deletions; 1/14 [7%] duplication; 3/14 [21%] inversions; 2/14 [14%] translocations. FISH was performed on 23 cases for reasons other than to characterize a previously identified cytogenetic abnormality. All 23 cases were negative. Fragile-X testing by Southern blots and PCR analysis found 7/316 [2.2 %] with an abnormal result. The mutations detected were: a full mutation (fM) and abnormal methylation in 3 [43 %], mosaic mutations with partial methylation of variable clinical significance in 3 [43%] and a permutation carrier [14%]. The frequency of chromosome and fragile-X abnormalities appears to be within the range in reported surveys (cs 4.8-1.7%, FRAX 2-4%). Limitations of our retrospective study include paucity of behavioral diagnostic information, and a specific clinical criterion for testing. CONCLUSIONS: Twenty-eight percent of chromosome abnormalities detected in our study were subtle; therefore a high resolution cytogenetic study with a scrutiny of 15q11.2q13, 2q37 and Xp23.3 region should be standard practice when the indication is autism. The higher incidence of mosaic fragile-X mutations with partial methylation compared to FRAXA positive population [50% vs 15-40%] suggests that faint bands and variations in the Southern band pattern may occur in autistic patients.

Autistic Disorder↗
PubMed1976

[Effects of lithium chloride administered in combination with methamphetamine or a reserpine- like drug on brain norepinephrine and dopamine metabolism in rats].

Lithium chloride (LiCl) was injected acutely (2.4 mEq/kg, i.p.) or subacutely (2.5 mEq/kg X 2/day for 4.5 days, i.p.) in rats treated concurrently with methamphetamine (MAPT) or a reserpine-like drug (Ro4-1284), and effects of LiCl on behavior as well as metabolism of brain norepinephrine (NE) and dopamine (DA) were investigated. Acute administration of LiCl suppressed the MAPT-induced hyper-locomotor activity but did not affect the Ro4-1284-induced behavioral depression. LiCl administered subacutely increased the MAPT-induced stereotyped behavior, and it reduced the Ro4-1284-induced initial transient excitation in spontaneous locomotor activity and tended to facilitate the recovery from behavioral depression. As for NE and DA metabolism, LiCl administered subacutely inhibited the MAPT-induced decrease of the deaminated NE metabolites and Ro4-1284-induced decrease of DA metabolism and the Ro4-1284-induced alterations in NE metabolism. From these results, it is likely that the inhibitory effect of LiCl on the MAPT and Ro-1284-induced changes in NE and DA metabolism may to some extent be involved in the therapeutic effects on manic-depressive illness.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1981

Investigations on behavioral effects of an extract of Cannabis sativa L. in the rat.

The behavioral responses of the rat to an extract of Cannabis sativa were examined after IP injection of 5, 15 and 30 mg/kg (expressed as delta 9 tetrahydrocannabinol). The lowest dose of the extract induced stereotyped behavior (rhythmic head movements, intermittent gnawing and sniffing) together with hypersensitivity to stimuli and hyperthermia. The administration of higher doses of the extract resulted, initially, in similar behavioral effects but of greater intensity, followed by a cataleptic state alternating with atonic muscular prostration; rectal temperature was decreased. Pre-treatment with 6-hydoxydopamine (6-OHDA, which produces degeneration of catecholamine-containing nerve terminals)or pimozide (blocker of dopamine receptors) significantly reduced both stereotype and hyperreactivity. Thermic effects were also antagonized by 6-OHDA pre-treatment. Cannabis-induced catalepsy was enhanced by pimozide but reduced by atropine (3 mg/kg SC). These results support the hypothesis that catecholamines play an important role in the complex behavioral effects of cannabis.

Animals↗
PubMed1977

[Rest-activity-cycle and stereotyped hand waving of a mentally defective child (author's transl)].

Stereotyped acts of a mentally defective girl. 6;6 years old, were observed from 6 a.m. till 8 p.m. during 16 days. Alternating phases of more or less frequent stereotyped hand waving showed a prominent periodicity of about 90 minutes. Sleep stages were also determined polygraphically during 10 nights. As statistically proved the mean peak-to-peak interval of the stereotyped activity at days corresponded to the mean REM- to REM period of nights. This suggests, that the stereotyped behavior of this child was driven by the basic rest activity cycle already described by Kleitman. The mean periodicity of sleep stages was represented by modeled rhythms adapted to the scored sleep stages. If the model rhythms of all 10 nights were extended backward to the preceding days, they paralleled the stereotyped activity. Half periods found in phase with REM stages corresponded to the maxima of the stereotyped activity. It will be discussed that the basic rest activity cycle triggers sensory as well as motor mechanisms characterizing both the phases of enhanced stereotyped activity and REM stages.

Behavior↗
PubMed1980

Observational studies of retarded children with multiple stereotyped movements.

Stereotyped movements, such as body rocking and hand gesturing, are common among developmentally delayed children. However, very little is known concerning the naturally occurring circumstances that produce variability in this type of responding. Three relatively long-term observational studies, involving seven preschool children, each of whom exhibited multiple stereotypies, were conducted to determine the extent to which the type of activity or setting had any effect upon the rates of these responses. Repeated observations were made of each child during a variety of school activities. In two studies, adult-child interactions were also recorded. The results showed that, in general, the particular activity greatly affected rates of stereotyped behavior, although there were some marked individual differences. Moreover, in two studies variability was apparent across sessions within a particular setting. For some of the children, there was evidence that their multiple stereotypies were functionally interrelated. Adult interactions, as recorded in one study, appear to be both quantitatively and qualitatively different for stereotyping as contrasted with nonstereotyping children. An environmental analysis employing a sequential model indicated that there were teacher behaviors that affected the frequency and/or conditional probability of the child's aberrant behavior.

Child↗
PubMed1982

Implications for multiple transmitter mediation of amphetamine-induced stereotypies.

Gerbils were pretreated with the dopamine (DA) receptor blocker, pimozide, prior to stereotypy-inducing injections of d-amphetamine. Some of the stereotypies induced with amphetamine were blocked, but some were not, supporting the hypothesis that multiple neurotransmitters are involved in the mediation of amphetamine-induced stereotypy. In addition, when apomorphine hydrochloride was injected, different stereotypic motor behaviors were induced than were induced with amphetamine. The behavioral changes following amphetamine treatment could be classified into four groups: (1) those that are probably DA related, based on the fact that they were induced with either amphetamine or apomorphine, and amphetamine induction was blocked with pimozide; (2) those that are probably not DA related because they were not induced by apomorphine, and amphetamine induction was not blocked by pimozide; (3) those behaviors that may be incompatible with stereotypic behaviors, were reduced with either amphetamine or apomorphine, but were not maintained with pimozide; and (4) circling, which was induced with amphetamine, blocked with pimozide, but not induced with apomorphine.

Animals↗