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PubMed1995

Empirically derived subtypes of pervasive developmental disorders: a cluster analytic study.

A cluster analytic study was conducted to empirically derive behaviorally homogeneous subtypes of pervasive developmental disorders (PDD). Subjects were clustered based on a broad range of behavioral symptoms which characterize autism. Behavioral variables were measured using several of the standardized psychometric instruments most commonly employed in assessing autistic individuals. The cluster solution indicated the presence of four distinct groups. Validity checks generally confirmed significant between-group differences on independent measures of social, language, and stereotyped behaviors. In addition, the four-group cluster solution was compared to previously developed typological systems of PDD (i.e., subcategories based on IQ early onset, styles of social interaction, and DSM-III-R diagnosis). Results generally supported both the behavioral homogeneity of the four subgroups and also several important between-group differences. The potential utility of using cluster analyses to explore subtypes of PDD is discussed.

Adolescent↗
PubMed1990

Innate learning preferences: signals for communication.

Research on the ways in which different species of birds learn to sing is used to illustrate the necessity of taking innate factors into account in studies of behavioral development. Experiments on two species of songbirds are described that reveal innate species differences in responsiveness to tape-recorded songs. Conspecific songs are favored over those of other species. These patterns of innately varying responsiveness provide a basis for the development, not of stereotyped behavior, but of variable, individually learned behavior. The viewpoint is presented that mechanisms that differ innately from species to species, some with general functions, others specialized for particular ontogenetic assignments, provide the necessary substrates with which experience interacts.

Animal Communication↗
PubMed1990

Apomorphine facilitates male sexual behavior of rhesus monkeys.

In the present study, a novel sexual behavior paradigm was used to study the effects of the dopamine agonist, apomorphine, on male sexual behavior of rhesus monkeys. In Experiment 1, the effects of apomorphine treatment were assessed by observing the behavioral responses of male rhesus to a sexually receptive female monkey that they could see, hear, and smell, but could not physically contact. Apomorphine treatment produced a spectrum of behavioral effects that differed depending on the dose of drug administered. Low doses of apomorphine (25-100 micrograms/kg) stimulated yawning, moderate doses (50-200 micrograms/kg) facilitated male sexual responses associated with the genitals including penile erection and masturbation, and high doses (greater than 200 micrograms/kg) elicited stereotypic behavior. Experiment 2 examined whether the behavioral responses of male monkeys to apomorphine treatment were influenced by the stimulus female. Apomorphine treatment facilitated penile erections in tests in which a stimulus female was present, but did not facilitate erections in tests in which she was absent. In sum, these experiments provide preliminary evidence that dopaminergic mechanisms may play a role in the regulation of male sexual behavior of rhesus monkeys.

Animals↗
PubMed1991

Chronic ascorbate potentiates the effects of chronic haloperidol on behavioral supersensitivity but not D2 dopamine receptor binding.

Ample behavioral evidence suggests that ascorbate parallels the action of haloperidol, a widely used neuroleptic. To determine the extent to which this parallel extends to chronic treatment, 21 days of exposure to ascorbate (100 or 500 mg/kg) alone or combined with haloperidol (0.5 mg/kg) were assessed on stereotyped behavior and neostriatal D2 dopamine receptor binding in rats. Our results indicate that when challenged with the dopamine agonist, apomorphine (0.5 mg/kg), animals chronically treated with haloperidol or high-dose ascorbate alone display a supersensitive sniffing response relative to controls, while animals chronically treated with the combination of haloperidol and high-dose ascorbate display a further potentiation of sniffing relative to the haloperidol groups. In addition, [3H]spiperone saturation studies showed, as expected, an up-regulation of striatal D2 dopamine receptors in rats treated with haloperidol as reflected by a change in receptor density (Bmax) but not affinity (KD). Ascorbate treatment, however, had no effect on D2 receptor density or the distribution of [3H]apomorphine in whole brain. Even though chronic treatment with the haloperidol-high-dose-ascorbate combination produced an up-regulation of striatal D2 dopamine receptors, this treatment did not cause a further up-regulation relative to haloperidol alone nor did it have any effect on [3H]apomorphine distribution. Taken together, these findings indicate that although chronic ascorbate produces behavioral supersensitivity to apomorphine through central mechanisms, they appear to differ from those induced by chronic haloperidol.

Amphetamines↗
PubMed2005

Alterations in striatal neuropeptide Y system activity of rats with haloperidol-induced behavioral supersensitivity.

The study was conducted to determine whether the expression of behavioral supersensitivity induced by haloperidol (HAL) administered once daily (2 mg/kg i.p.) for 14 days is associated with the alterations in activity of neuropeptide Y (NPY) system in the striatum (caudate-putamen) and nucleus accumbens. Dopamine supersensitivity was tested by measurement of locomotor activity and stereotyped behavior after administration of the dopamine D2/D3 receptor agonist quinpirole (1 mg/kg i.p.) on day 1, 3 and 7 after HAL withdrawal. Neuropeptide Y-like immunoreactivity (NPY-LI) was determined in the striatum and nucleus accumbens isolated 6 h after quinpirole injection on day 1, 3 and 7 after the end of HAL treatment. NPY mRNA was quantified in these structures on day 7 after HAL withdrawal. HAL increased spontaneous locomotor activity and prevalence of rearing, grooming and head-down sniffing. At the same time, striatal NPY-LI increased progressively from the reduced level found on day 1 of haloperidol withdrawal. NPY mRNA remained unchanged. In saline-treated rats, quinpirole enhanced locomotion, rearing, and induced intense head-down sniffing and oral activity. These behavioral effects were accompanied by a decrease in striatal NPY-LI. NPY mRNA was slightly increased. HAL treatment altered response to quinpirole, namely it increased locomotion, intensified oral activity and reduced rearing and head-down sniffing. The second and the third quinpirole injection decreased NPY-LI levels. NPY mRNA was unchanged. In the nucleus accumbens, apart from a decrease in NPY-LI on day 1 after the last haloperidol dose, the level of NPY-LI and NPY mRNA in any experimental group did not differ from the control value. The presented results suggest that the alterations in the activity of the striatal but not nucleus accumbens NPY system contribute to adaptive changes induced by long-term haloperidol treatment and may be of significance to the motor hyperactivity induced by intermittent stimulation of postsynaptic dopamine D2 receptors.

Animals↗
PubMedDate not supplied

[Behavioral and neuronal effects of visual deprivation in cats].

Recent data obtained in the Nencki Institute are reviewed. In the cats deprived of pattern vision from birth several deficits were observed: (I) A simultaneous object discrimination learning for food reward was strongly impaired. However, retention of discrimination was only slightly impaired by bisual cortex ablation. (II) Ocular following reflex was impaired. (III) In the living cages stereotyped behavior appeared. (IV) Direction selectivity of superior colliculus units was impaired. (V) Percentage distribution of insoluble proteins in the electrophoretic pattern from visual and somatic sensory cortex was affected.

Animals↗
PubMed1975

Drug-induced dyskinesia in monkeys.

Easily definable dyskinetic syndromes have been produced by injection of L-DOPA, apomorphine, trivastal, carbachol, sodium azide, tetrahydrocannabinol, phenothiazines, and amphetamines into one or more sites. Three species of monkeys have been used: rhesus, green, and squirrel. The descriptive information available on each of these dyskinetic syndromes indicates a striking degree of similarity among the effects of these various drugs and combinations of drugs. The behavior patterns produced can be roughly divided into three areas: (1) increased movement (hyperkinesia) and vigilance, determined at least in part by the area in which the animal is confined; (2) a wide range of adventitious movements of extremities, as well as face and tongue; and (3) "stereotypic" behavior, sometimes destructive, such as grooming, biting, and drinking. None of the above studies or models has been employed in monkeys free-ranging in open areas with other animals. It might be expected that the effects of the drugs would be somewhat already by the social setting of the animal. It now seems adequately confirmed that the production of dyskinesia in monkeys is biochemically related to dopaminergic systems in the neostriatum. The evidence at present also points to a form of denervation hypersensitivity as the basis for the production of these syndromes in patients with dyskinesias on L-DOPA therapy (Chase, Holden, and Brody, 1972), although it is clear that in relatively high doses these drugs regularly produce dyskinesias in primates having no anatomical or biochemical pathology in the nervous system. These drug-induced dyskinesias in monkeys, especially those produced by L-DOPA in combination with other drugs or with anatomical and biochemical stereotaxically placed lesions, appear to be developed to a degree to be useful in the further evaluation of the mechanisms of dyskinesias in humans as well as providing methods of testing the effectiveness of various forms of therapy.

Amphetamine↗
PubMed1991

Autistic features in Joubert syndrome: a genetic disorder with agenesis of the cerebellar vermis.

Recent reports in the literature have suggested a link between abnormalities of the cerebellar vermis and the behavioral syndrome of autism. Joubert syndrome is an autosomal recessive disorder characterized by partial or complete agenesis of the cerebellar vermis. However, there is little behavioral or psychiatric description of patients with this genetic condition. In this report, the neuropsychiatric characteristics of two children with Joubert syndrome are described in detail. One child met DSM-III-R diagnostic criteria for autistic disorder, while the other displayed autistic features. The female child displayed stereotypic behavior and impairments in social interaction and communication, had a markedly restricted repertoire of interests, and showed distress over changes in the environment. The male child demonstrated perseveration and preoccupation with sounds and textures, but had no abnormalities in social interaction. Although both children showed developmental disabilities, the degree of cognitive delay was significantly less than that described in previous reports of children with Joubert syndrome. This report adds to the growing body of evidence implicating cerebellar involvement in developmental disabilities and autistic behavior.

Autistic Disorder↗
PubMed1996

The effects of chronic naltrexone treatment in young autistic children: a double-blind placebo-controlled crossover study.

In a double-blind placebo-controlled crossover trial 23 autistic children, aged 3-7 years, were treated with a mean daily dosage of 1 mg/kg naltrexone for 4 weeks. Drug effects were monitored with behavior checklists rated by parents and teachers, and ethological playroom observations. On average, parents' checklists and playroom data could not differentiate between naltrexone treatment and placebo treatment; however, teachers significantly favored naltrexone treatment. They reported a decrease in hyperactivity and irritability. No effects of naltrexone on social and stereotypic behavior could be demonstrated.

Autistic Disorder↗
PubMedDate not supplied

Effect of desipramine during infancy and preweanling on dorsal striatal dopamine D1 and D2 receptor binding in adolescence in the rat.

Desipramine, a monoamine uptake inhibiting antidepressant, was given once a day sc from the 6th to the 22nd postnatal days, which is during infancy and preweanling in ontogenesis, to rats and its effects on dorsal striatal dopamine D1 and D2 receptor binding in adolescence were examined. The rats were decapitated, their dorsal striata were dissected on approximately the 34th postnatal day, and the maximal densities (Bmax) and affinities (Kd) of dopamine D1 and D2 receptors were assayed using [3H] SCH 23390 and [3H] spiperone as ligands. Desipramine did not affect the densities or affinities of dopamine D1 or D2 receptor binding, and tended to increase the D1/D2 density ratio. The Bmax of dopamine D2 receptors was higher in male than in female rats (p<0.01), the D1/D2 Bmax ratio tended to be lower in male than in female rats (p<0.07), and the Kd for D1 receptors tended to be lower in male than in female rats (p<0.05). There was no interaction between treatment and gender. We conclude that desipramine given at infancy and preweanling increases the susceptibility of adolescent rats to behavioral effects of dopamine agonists with an optimal, and relatively high SCH 23390/spiperone binding site density ratio. Furthermore, gender differences in dorsal striatal spiperone binding site densities, SCH 23390/spiperone density ratio, and SCH 23390 affinities may render male rats more vulnerable than female rats to expression of excessive stereotyped behavior.

Adrenergic Uptake Inhibitors↗
PubMed1990

Voluntary consumption of beverage alcohol by vervet monkeys: population screening, descriptive behavior and biochemical measures.

Seventeen percent of 196 feral vervet monkeys (Cercopithecus aethiops) spontaneously drank appreciable quantities of beverage alcohol in 3% sucrose in preference to 3% sucrose alone. Ethanol consumption increased over time, as did the concentration of ethanol tolerated. Willingness to select ethanol was stable over a three-year period, as measured by periodic retesting. Individual patterns of drinking and behavioral responses to ethanol were quite variable. Upon occasion, some animals drank to ataxia and unconsciousness; signs of withdrawal, including tremulousness, pacing, irritability and increased aggression, followed the abrupt discontinuation of ethanol availability. A variety of changes in social interaction, including increased orientation to external stimulus, increased incidence of stereotyped aggression and of other stereotyped behaviors and decreased frequency of affiliative behaviors were observed during ethanol periods, as compared to baseline scoring periods. In a small number of alcohol-preferring animals, CSF amine metabolites (5-hydroxyindoleacetic acid and homovanillic acid) were raised by drinking alcohol. These studies suggest that the alcohol-selecting vervet monkey may be complementary to established primate models of alcoholism.

Alcohol Drinking↗
PubMed2001

Motoric behavior in aged rats treated with GM1.

Aging is associated with impaired motor function. Nigrostriatal dopaminergic neurons, in part, regulate motoric behavior, and undergo degenerative changes during aging. GM1 ganglioside partially restores pre-synaptic dopaminergic markers and the number and morphology of dopaminergic neurons in the midbrain and striatum of Sprague--Dawley aged rats. These studies investigated whether GM1 treatment, 30 mg/kg, i.p. daily for 36 days, affects locomotor and stereotypic activity, as well as coordination, balance, and strength in aged rats. Under the treatment conditions used, GM1 did not improve the reduced locomotor and stereotypic behavior of the aged rats. While it partially improved performance on a square bridge test, GM1 had no effect on inclined screen and rod suspension tests. Although GM1 restored the decreased content of dopamine and homovanillic acid in the nigrostriatal neurons of the aged rats, it had no effect on the reduced D1 and D2 dopamine receptor binding and mRNA in the striatum. It appears, that despite the morphological and metabolic restoration of aged nigrostriatal neurons, GM1 has limited ability in improving age-associated motor deficits.

Aging↗
PubMed2000

Network architectures and circuit function: testing alternative hypotheses in multifunctional networks.

Understanding how species-typical movement patterns are organized in the nervous system is a central question in neurobiology. The current explanations involve 'alphabet' models in which an individual neuron may participate in the circuit for several behaviors but each behavior is specified by a specific neural circuit. However, not all of the well-studied model systems fit the 'alphabet' model. The 'equation' model provides an alternative possibility, whereby a system of parallel motor neurons, each with a unique (but overlapping) field of innervation, can account for the production of stereotyped behavior patterns by variable circuits. That is, it is possible for such patterns to arise as emergent properties of a generalized neural network in the absence of feedback, a simple version of a 'self-organizing' behavioral system. Comparison of systems of identified neurons suggest that the 'alphabet' model may account for most observations where CPGs act to organize motor patterns. Other well-known model systems, involving architectures corresponding to feed-forward neural networks with a hidden layer, may organize patterned behavior in a manner consistent with the 'equation' model. Such architectures are found in the Mauthner and reticulospinal circuits, 'escape' locomotion in cockroaches, CNS control of Aplysia gill, and may also be important in the coordination of sensory information and motor systems in insect mushroom bodies and the vertebrate hippocampus. The hidden layer of such networks may serve as an 'internal representation' of the behavioral state and/or body position of the animal, allowing the animal to fine-tune oriented, or particularly context-sensitive, movements to the prevalent conditions. Experiments designed to distinguish between the two models in cases where they make mutually exclusive predictions provide an opportunity to elucidate the neural mechanisms by which behavior is organized in vivo and in vitro.

Animals↗
PubMed1996

Thyrotropin releasing hormone injected into the nucleus accumbens septi selectively increases face grooming in rats.

The effect of unilateral injection of peptides into the nucleus accumbens septi (NAS) on subcategories of grooming behavior was studied in male rats. The peptides used were: thyrotropin releasing hormone (TRH), luteinizing hormone releasing hormone (LHRH) and corticotropin releasing hormone (CRH). Male rats (Holtzman strain, 240-270 g body weight) injected with progressive doses of TRH (100, 200 and 400 ng) at 5-day intervals were compared with the control state (injection of artificial cerebrospinal fluid, CSF). A selective increase in face grooming was observed with the 100 ng (49.78 +/- 6.11, N = 18) and 200 ng (50.29 +/- 7.72, N = 17) doses of TRH (P < 0.05 vs CSF injection, 26.94 +/- 3.64, N = 18). Face grooming increased further with the 400 ng dose (55.19 +/- 8.26, N = 16, P < 0.01), but a dose-response curve could not be obtained at the dose range used. Flank scratching, head, body and genital grooming were not altered by the TRH injection, but the rearing behavior was inhibited (10.33 +/- 1.56; N = 18; 10.76 +/- 1.77, N = 17; 12 +/- 2.06, N = 16) (P < 0.05 for all doses vs controls, 20.61 +/- 2.81, N = 18). The rats that received LHRH (75 ng, N = 16) and CRH (100 ng, N = 14) did not show behavioral changes when compared with their control states. The results show that injection of TRH into the NAS, but not the injection of LHRH or CRH, selectively increases face grooming without affecting other subcategories of grooming at the doses used, and appears to link this peptide with the neural substrate of stereotyped behavior.

Animals↗
PubMed1998

The cold plate as a test of nociceptive behaviors: description and application to the study of chronic neuropathic and inflammatory pain models.

A cold plate apparatus was designed to test the responses of unrestrained rats to low temperature stimulation of the plantar aspect of the paw. At plate temperatures of 10 degrees C and 5 degrees C, rats with either chronic constriction injury (CCI) of the sciatic nerve or complete Freund's adjuvant (CFA) induced inflammation of the hindpaw displayed a stereotyped behavior. Brisk lifts of the treated hindpaw were recorded, while no evidence of other nociceptive behaviors could be discerned. The most consistent responses were obtained with a plate temperature of 5 degrees C in three 5-min testing periods, separated by 10-min intervals during which the animals were returned to a normal environment. Concomitantly to cold testing, the rats were evaluated for their response to heat (plantar test) and mechanical (von Frey hairs) stimuli. In both injury models, while responses to heat stimuli had normalized at 60 days post-injury, a clear lateralization of responses to cold was observed throughout the entire study period. Systemic lidocaine, clonidine, and morphine suppressed responses to cold in a dose-related fashion. At doses that did not affect motor or sensory behavior, both lidocaine and its quaternary derivative QX-314 similarly reduced paw lifts, suggesting that cold hyperalgesia is in part due to peripheral altered nociceptive processing. Clonidine was more potent in CCI then in CFA rats in reducing the response to cold. Paradoxically, clonidine increased the withdrawal latencies to heat in the CCI hindpaw at 40 days and thereafter, at a time when both hindpaws had the same withdrawal latencies in control animals. Morphine was also more potent on CCI than CFA cold responses, indicating that, chronically, CFA-induced hyperalgesia might be opiate resistant. Evidence for tonic endogenous inhibition of cold hyperalgesia was obtained for CFA rats, when systemic naltrexone significantly increased the number of paw lifts; this was not found in rats with CCI. At 60 days, neither morphine nor naltrexone affected cold-induced paw lifting in CFA rats, suggesting that the neuronal circuit mediating cold hyperalgesia in these animals had become opiate insensitive. In conclusion, the cold plate was found to be a reliable method for detecting abnormal nociceptive behavior even at long intervals after nerve or inflammatory injuries, when responses to other nociceptive stimuli have returned to near normal. The results of pharmacological studies suggest that cold hyperalgesia is in part a consequence of altered sensory processing in the periphery, and that it can be independently modulated by opiate and adrenergic systems.

Analgesics, Opioid↗
PubMed1990

Potentiation of yawning responses to the dopamine receptor agonists B-HT 920 and SND 919 by pindolol in the rat.

Subcutaneous injection of B-HT 920, a dopamine D2-receptor agonist, in doses ranging from 5 to 100 micrograms/kg, induced yawning behavior in rats. Yawning was also elicited by low doses (25-500 micrograms/kg sc) of SND 919, a newly synthesized dopamine receptor agonist. The yawning evoked by B-HT 920 or SND 919 was increased by the beta-adrenoceptor antagonist pindolol (20 mg/kg ip) which alone did not induce yawning. Stereotyped behavior did not appear after B-HT 920 or SND 919 given alone or in combination with pindolol. The results suggest that SND 919 as well as B-HT 920 has stimulatory activity at dopamine D2-receptors, and that pindolol may exert its enhancement of the yawning response to dopamine receptor agonists via blockade of beta-adrenoceptors.

Adrenergic beta-Antagonists↗
PubMed1986

Locomotor behaviors in response to new selective D-1 and D-2 dopamine receptor agonists, and the influence of selective antagonists.

With the introduction of the selective D-1 dopamine receptor agonist and antagonist benzazepines, especially as enantiomeric pairs, there is now a range of D-1 compounds to complement the previously available selective D-2 agents. These have been used to investigate whether sub-types of dopamine receptors might be differentially involved in locomotor behavior. Stereotyped locomotion induced by the non-selective D-2 agonist apomorphine and by the selective D-2 agonist RU 24213 were blocked by the selective D-2 antagonists metoclopramide and Ro 22-2586 [-)-piquindone). Responses to either D-2 agonist were also blocked by the selective D-1 antagonists SCH 23390 and R-(but not S-) SK&F 83566. Non-stereotyped locomotion was induced by R- but not S-SK&F 38393, a stereoselective D-1 agonist, and was blocked by SCH 23390. Responses to the D-1 agonist were also antagonised by metoclopramide. Such results suggest concerted D-1:D-2 interplay in the regulation of at least some dopaminergic behaviors, such as locomotion.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2004

Risperidone reduction of amphetamine-induced self-injurious behavior in mice.

The behavioral and neurochemical effects of high doses of amphetamine administered to BALB/c mice were examined in the presence and absence of co-administered haloperidol (a D2 antagonist), SCH 23390 (a D1 antagonist) and risperidone (a mixed 5-HT2/D2 antagonist). It was observed that mice displayed a dose-dependent increase in stereotypic behavior, oral dyskinesia, and self-injurious behavior (SIB) in response to amphetamine treatment. Furthermore, agents that blocked the SIB reversed the amphetamine-induced release of serotonin. This effect was unrelated to hyperthermia or non-specific sedation (as assessed by measurement of motor activity). These data are interpreted in the context of the underlying basis of murine SIB involving both dopaminergic and serotonergic activation and demonstrate the efficacy of risperidone in treating these behaviors.

Amphetamine↗