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PubMed1989

Neurochemical mechanisms involved in behavioral effects of amphetamines and related designer drugs.

The motor activation produced by psychomotor stimulants has been long associated with the midbrain dopamine systems. While focused stereotyped behavior produced by high doses of indirect sympathomimetics is blocked by removal of dopamine terminals in the corpus striatum (Creese and Iversen 1975), the locomotor activation produced by low doses of indirect sympathomimetics is blocked by removal of dopamine terminals in the region of the nucleus accumbens (Kelly et al. 1975). This dopaminergic substrate for psychostimulant effects appears selective for the indirect sympathomimetics in that dopamine lesions to the region of the nucleus accumbens do not block caffeine, scopolamine, heroin, or CSF-induced locomotor activation (Swerdlow and Koob 1985; Vaccarino et al. 1986). The neurochemical sites for psychomotor stimulant reward are likely to be the presynaptic dopamine terminals located in the region of the nucleus accumbens, frontal cortex, and other forebrain structures that originate in the ventral tegmental area. Note, however, that intracranial self-administration of cocaine is elicited from the frontal cortex, but not from the nucleus accumbens (Goeders and Smith 1983). Thus, concomitant activation of structures other than the nucleus accumbens may be an important part of the circuitry involved in initiation of cocaine intravenous self-administration, as has been hypothesized for the opiates (Smith and Lane 1983; Smith et al. 1982). In addition, these neuropharmacological studies provide evidence to show that, in the rat, the neural/neurochemical substrates for processing the reinforcing and stimulant properties of psychomotor stimulants may be similar, if not identical. Parallel manipulations using dopamine receptor antagonists and 6-OHDA lesions produce parallel results. How far this parallelism continues in further processing is under current investigation; however, such an overlap brings additional impetus to earlier hypotheses relating reinforcement and motor function (Glickman and Schiff 1967). The motor activation produced by MDMA and MDE has similarities to classic psychostimulants, but also some important differences. In the BPM system, the stimulant-like properties of these drugs were reflected in significant increases in horizontal locomotor activity measured across a wide dose range. Interestingly, medium to high doses of MDMA or MDE produced a transient decrease in horizontal locomotion for the first 10 minutes, followed by a sustained increase. The increase in holepokes and rearings that typically accompanies the increase in ambulation seen with amphetamine itself or other indirect sympathomimetics (Geyer et al. 1986) was not observed with MDMA or MDE.(ABSTRACT TRUNCATED AT 400 WORDS)

Amphetamines↗

PubMed1988

Behavioral and neurochemical effects of intraperitoneally injected dendrotoxin.

Intraperitoneal administration of dendrotoxin, a polypeptide isolated from Dendroaspis angusticeps venom, provoked in mice the appearance of a complex stereotyped behavior including biting, head nodding, 'wet-dog' shakes and rearing. Signs of autonomic hyperactivity as well as hyperreactivity to sound and touch were prominent. Neurochemical analyses of monoamines and monoamine metabolites showed no change 90 min after dendrotoxin, with a decrease in dopamine concentrations and an increase in their metabolites in the striatum starting 3 hr later. Moreover, at this time, dendrotoxin also produced a significant increase of 5-hydroxytryptamine metabolites. These data are interpreted as indicating that dendrotoxin crosses the blood-brain barrier and provokes an increase of the activity at monoaminergic terminals.

Animals↗

PubMed1988

Clinical effects of fenfluramine on children with autism: a review of the research.

A review of research studies published to date on the effects of fenfluramine on children with autism is presented. The current status of the fenfluramine research on children with autism is assessed. The review analyzed the methodological aspects of the research, the toxicity of fenfluramine, and the relationship between fenfluramine, neurotransmitter activity, cognitive ability, and subsequent behavioral change. The review of published data indicated that fenfluramine had positive effects on the reduction of hyperactivity and stereotypic behaviors in 33% of the subjects. The best responders were children with the highest baseline IQs. The conclusions address the need for appropriate subgrouping of autistic syndromes, which may lead to identification of responders to pharmacological treatments. The need for further study of the possible long-term adverse side effects of flenfluramine is noted. Further experimental research on the effects of fenfluramine on children with autism is endorsed.

Adolescent↗

PubMed1979

Local hormonal modulation of neural activity in Aplysia.

The abdominal ganglion of Aplysia provides a convenient experimental system for cellular studies on the roles of peptides as chemical messengers in the nervous system. There are indications that the bag cells, a group of neuroendocrine cells, synthesize and release egg laying hormone (ELH), a peptide with an apparent molecular weight of 6000. Our recent investigations indicate that a burst of impulse activity in the bag cells produces five types of long-lasting responses, some excitatory, others inhibitory, in 26 identified neurons and 2 identified cell clusters located near the bag cells in the abdominal ganglion. The responses have slow, smoothly graded onsets, and many of them result in modulation of neuronal activity for 3 hours or more. Physiological and ultrastructural data support the hypothesis that they are induced by a bag cell hormone (or hormones) that is released into vascular and interstitial spaces of the ganglion to act on the target neurons. Local application of purified ELH to one of the target neurons provides evidence that the bag cell effect is mediated by ELH. Many of the target neurons are known to be parts of neuronal circuits that control specific behavioral and homeostatic processes. Since egg laying is initiated by the bag cell discharge and is associated with a stereotyped behavior pattern lasting several hours, the actions of these peptide-secreting neurons on the central nervous system may serve to regulate certain elements of behavior and homeostasis during egg laying.

Animals↗

PubMedDate not supplied

Catalepsy and hyperkinesis induced by the chronic injection of a tetrapeptide into the neostriatum.

The influence on behavior of the chronic (over the course of three weeks) injection of leu-enkephalin and its analog, a tetrapeptide, in doses of 5 and 15 micrograms, into the neostriatum was investigated in experiments on rats. Native enkephalin had little effect, but the tetrapeptide in both doses blocked conditioned reflex avoidance behavior and induced a set of complex changes in behavior. Catalepsy with pronounced waxy rigidity of the skeletal musculature was the main element of the pathological behavior. Stereotypical slow movements of the head and forelimbs began to predominate on the second week of the microinjections. Changes in behavior but without catalepsy and hyperkinesis were observed on the following days. It is hypothesized that the phenomena described are associated with reorganizations of neuromediator systems that accompany the chronic influence on the opiate system of the neostriatum. The role of the enkephalinergic system in the genesis of psychomotor deviations is discussed, as well as the possibility of obtaining through the method utilized of models of neurological and psychopathological deviations.

Animals↗

PubMed1979

Comparison of behavioral effects of systemic L-DOPA and intracranial dopamine in mesolimbic forebrain of nonhuman primates.

The systemic administration of L-DOPA and carbidopa to six rhesus and four squirrel monkeys produced an initial period of depressed activity followed by increased locomotion, hypervigilance, involuntary oral-facial movements and a gnawing syndrome. The squirrel monkey exhibited a depressed phase, locomotor stimulation, searching behavior, stereotypic grooming and gnawing syndrome. Most of these activities were prevented by pretreatment with 0.1 mg/kg haloperidol. Bilateral injection of 100 microgram dopamine into the mesolimbic forebrain of four squirrel monkeys also produced an initial depression followed by hyperactivity similar to that produced by L-DOPA, but without gnawing. A stereotyped submissive or juvenile posturing occurred in three animals. These DA-induced activities were blocked by 0.1 mg/kg haloperidol. Similar injection of 100 microgram L-norepinephrine produced a profound depression followed by moderate activity coupled with loss of extensor muscle strength in the legs. Bilateral injection of 300 microgram dopamine into the nucleus accumbens of a rhesus monkey produced stereotypic pacing. These data confirm in primates the importance of dopaminergic mechanisms of the mesolimbic forebrain in locomotor activity and behavior.

Animals↗

PubMed1978

Responses of boys and girls to aggressive, assertive, and passive behaviors of male and female characters.

Boys and girls in grades 4, 6, and 8 answered five questions after reading stories in which a male or female character behaved aggressively, assertively, or passively. As hypothesized, the results indicated differential degrees of approval for aggressive, assertive, and passive behavior depending upon the sex of the character engaged in the behavior. Boys and girls also responded in different ways to the three types of behavior. Developmental trends indicated an increasingly positive evaluation of the effectiveness of passive behavior by females and an increasingly negative evaluation by males with age. The implications for the acquisition of sex-stereotyped behavior patterns are discussed.

Adolescent↗

PubMedDate not supplied

[The effect of alcoholization on the behavioral reactions of rats in an 8-arm radial maze].

The influence of 20% alcohol consumption on training of low-active rats in 8-arm radial maze was studied. One group of animals was trained before and the other group after the alcoholization. All the animals acquired the conditioned reaction in the radial maze. However, the behavioral difference between the groups consisted in spatially-motor asymmetry. The rats trained before the alcohol consumption had less stereotyped behavior and more distinctly preferred to enter the maze arms at the angle of 45 degrees than the animals trained after the alcohol consumption. After the alcohol consumption, rats more frequently refused from behavioral task performance in comparison with the animals trained after the alcoholization. The influence of alcohol consumption of learning and memory in low-active rats is discussed.

Alcohol Drinking↗

PubMed2000

[Neuropsychology of frontal type dementia].

The clinical conceptual change in frontal type dementia is reviewed in discussing its relationships to several related concepts such as Pick's disease, frontotemporal dementia (FTD), semantic dementia (SD) and frontotemporal lobar degeneration. We analyzed frontal type dementia selected from a consecutive series of our outpatients as to the details of neuropsychological symptoms, psychiatric symptoms, and abnormal behaviors. In our series of 143 patients with primary degenerative dementia, there were 16 cases of FTD and 6 cases of SD. Patients with two types of FTD and patients with SD were not distinguishable by neuropsychological examinations, behavioral abnormalities and psychiatric symptoms assessed with the Neuropsychiatric Inventory except for aphasia. The clinical picture of frontal type dementia involves frontal lobe symptoms such as disinhibition, apathy and stereotypy. Semantic memory loss for words, objects or faces suggestive of temporal lobe involvement developed only in patients with SD, and not in patients with FTD. Certain behavioral symptoms seen in frontal type dementia may respond to selective serotonin reuptake inhibitors. In care for patients with frontal type dementia, behavioral disturbances can be diminished and the quality of life can be improved by using their preserved procedural memory, pathological stereotypic behavior and stimulus-bound behavior such as utilization behavior and environmental dependency syndrome.

Dementia↗

PubMed1998

Time course of the development of motor behaviors in the zebrafish embryo.

The development and properties of locomotor behaviors in zebrafish embryos raised at 28.5 degrees C were examined. When freed from the chorion, embryonic zebrafish showed three sequential stereotyped behaviors: a transient period of alternating, coiling contractions followed by touch-evoked rapid coils, then finally, organized swimming. The three different behaviors were characterized by video microscopy. Spontaneous, alternating contractions of the trunk appeared suddenly at 17 h postfertilization (hpf), with a frequency of 0.57 Hz, peaked at 19 hpf at 0.96 Hz, and gradually decreased to <0.1 Hz by 27 hpf. Starting at 21 hpf, touching either the head or the tail of the embryos resulted in vigorous coils. The coils accelerated with development, reaching a maximum speed of contraction before 48 hpf, which is near the time of hatching. After 27 hpf, touching the embryos, particularly on the tail, could induce partial coils (instead of full coils). At this time, embryos started to swim in response to a touch, preferentially to the tail. The swim cycle frequency gradually increased with age from 7 Hz at 27 hpf to 28 Hz at 36 hpf. Lesions of the central nervous system rostral to the hindbrain had no effect on the three behaviors. Lesioning the hindbrain eliminated swimming and touch responses, but not the spontaneous contractions. Our observations suggest that the spontaneous contractions result from activation of a primitive spinal circuit, while touch and swimming require additional hindbrain inputs to elicit mature locomotor behaviors.

Aging↗

PubMed2002

Autism and gastrointestinal symptoms.

Autism is a collection of behavioral symptoms characterized by dysfunction in social interaction and communication in affected children. It is typically associated with restrictive, repetitive, and stereotypic behavior and manifests within the first 3 years of life. The cause of this disorder is not known. Over the past decade, a significant upswing in research has occurred to examine the biologic basis of autism. Recent clinical studies have revealed a high prevalence of gastrointestinal symptoms, inflammation, and dysfunction in children with autism. Mild to moderate degrees of inflammation were found in both the upper and lower intestinal tract. In addition, decreased sulfation capacity of the liver, pathologic intestinal permeability, increased secretory response to intravenous secretin injection, and decreased digestive enzyme activities were reported in many children with autism. Treatment of digestive problems appears to have positive effects on autistic behavior. These new observations represent only a piece of the unsolved autism "puzzle" and should stimulate more research into the brain-gut connection.

Acetaminophen↗

PubMed2006

One-sided limb preference is linked to alternating-limb locomotion in anuran amphibians.

Amphibians provide a unique opportunity for identifying possible links between lateralized behaviors, locomotion, and phylogeny and for addressing the origin of lateralized behaviors of higher vertebrates. Five anuran species with different locomotive habits were tested for forelimb and hind limb preferences during 2 stereotyped behavior sequences--wiping a foreign object off their snout and righting themselves from the overturned position. The experiments were analyzed in a broader context of previous findings on anuran lateralization involving 11 anuran species that were studied within the same experimental paradigms. This analysis shows that one-sided forelimb and hind limb motor lateralization in anurans is strongly associated with alternating-limb locomotion and other unilateral limb activity. Conclusions reached for anuran amphibians may be applicable to other vertebrates possessing paired appendages-the degree of lateralization in motor response depends on the mode of locomotion used by a species.

Amphibians↗

PubMed2000

The effects of DCG-IV and L-CCG-1 upon phencyclidine (PCP)-induced locomotion and behavioral changes in mice.

The behavioral changes of mice induced by acute and repeated i.p. injection of phencyclidine (PCP) were observed by measuring locomotor activity and stereotyped behavior. Then, the effects of metabotropic glutamate receptor (mGluR) agonists, DCG-IV and L-CCG-1, on the above behavioral changes induced by PCP were found. The effects of DCG-IV were very strong and completely depressed the PCP-induced hyperlocomotion. The effects of L-CCG-1 were not so strong. Repeated injection of PCP for 20 days into mice induced lower locomotor activity than that in acutely injected mice. These behavioral changes may be related with the negative symptoms of schizophrenia. In order to examine some molecular mechanisms of PCP-induced behavioral changes, Northern blot analysis of total RNA from prefrontal cortical tissues of mice treated with PCP, DCG-IV, and L-CCG-1 was carried out.

Amino Acids, Dicarboxylic↗

PubMed1989

[Adaptive changes in sigma and phencyclidine receptors during the long-term use of haloperidol and raclopride in rats].

The experiments on male albino rats have shown that 15 days haloperidol (0.5 mg/kg) and raclopride (1 mg/kg) treatment, but not acute administration, causes the increase of density of sigma receptors in the brain. The number of phencyclidine receptors was also elevated, but this increase was not statistically evident. The behavioral effects of ketamine (5 mg/kg) were evidently decreased after long-term haloperidol and raclopride treatment. The motor stimulation and stereotyped behavior induced by apomorphine (0.15 mg/kg) were increased only after treatment of haloperidol, but not raclopride. It seems probable that repeated neuroleptic (haloperidol and raclopride) treatment causes the hyposensitivity of sigma and phencyclidine receptors, despite the increase of their number. It is possible that this change is related to the depolarization inactivation of dopamine neurons caused by repeated neuroleptic administration.

Adaptation, Physiological↗

PubMed1997

Behavior therapy empowers persons with severe mental illness.

Behavior therapy has been viewed by some as disempowering persons with severe mental illness (i.e., undermining their ability to make independent decisions). This is ironic because various behavioral strategies actually promote independent decision making. Behavioral interventions (a) provide a safe place for persons to consider their life decisions; (b) simplify the range of choices that comprise many of these decisions; (c) help persons with severe mental illness learn behaviors so that they can better meet the demands of independent decision making: (d) teach family members skills so that they can provide more resources to support independent decision making; and (e) facilitate self-control over behaviors and the settings in which they occur. Behavior therapists need to assert the important role that behavioral principles assume in empowering persons with mental illness so that these principles are not discarded by professionals who misunderstand, or otherwise stereotype, behavioral interventions.

Behavior Therapy↗

PubMed2004

Striatal microinfusion of Tourette syndrome and PANDAS sera: failure to induce behavioral changes.

Rodent striatal microinfusions have been suggested as a model for assessing the behavioral effects induced by antineuronal antibodies. We used this approach to evaluate the proposed autoimmune etiology for Tourette syndrome (TS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Sera were assessed from patients with TS (n = 9) preselected based on the presence of elevated enzyme-linked immunosorbent assay optical densities against putamen homogenate and sera from patients with PANDAS (n = 8), selected from a larger group assayed for antibodies against a putamen synaptosomal preparation. The effect of antibodies against the streptococcal M5 protein were also studied. A total of 44 Fischer rats received bilateral infusion of sera: 23 ventral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 8 control); 21 ventrolateral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 6 controls). Cannulas were placed bilaterally and symmetrically by stereotactic techniques. After animals were allowed to recover for 1 week, sera were microinfused for 3 days. Animal behavior was then simultaneously quantified by daily observation and monitoring using automated activity boxes for 10 days after infusion. No significant alterations in stereotypic behavior or movement were observed between the PANDAS, TS, or anti-M5 protein and control groups. Our findings are in contrast to previous reports, and suggest the need for further investigations to determine the validity of the model and of autoimmune-mediated hypotheses for pediatric movement disorders.

Animals↗

PubMed1999

Effects of continuous exposure to light on behavioral dopaminergic supersensitivity.

BACKGROUND: This study examines the effects of long-term continuous exposure to light on dopaminergic supersensitivity induced by repeated treatment with haloperidol in rats. METHODS: Spontaneous general activity in an open-field (SGA) and stereotyped behavior induced by apomorphine (SB-APO) or amphetamine (SB-AMP) were used as experimental parameters. Rats were allocated to four groups in each experiment: saline-treated animals kept under a 12-hour light/dark cycle (LD) or 24-hour light/light cycle (LL), and 2 mg/kg haloperidol-treated animals kept under the above cycles. Plasma corticosterone concentration was also measured by radioimmunoassay in saline-treated rats kept under a LD or LL cycle. RESULTS: All the behavioral parameters used showed the development of central dopaminergic supersensitivity in rats kept under both cycles. Continuous exposure to light enhanced SGA and SB-AMP in both saline- and haloperidol-treated rats, but did not modify SB-APO. Animals kept under the LL cycle presented an increased plasma corticosterone concentration. CONCLUSIONS: Our results suggest that continuous exposure to light leads to an increase in dopaminergic function in both normal and "supersensitive" rats. This effect seems to be mediated by a presynaptic mechanism possibly involving corticosterone actions.

Animals↗

PubMed2005

2-Phenylethylamine in combination with l-deprenyl lowers the striatal level of dopamine and prolongs the duration of the stereotypy in mice.

2-Phenylethylamine (PEA)-induced stereotypy in rodents is suggested to model psychotic symptoms of schizophrenia. It is reported that PEA induces dopamine release in the striatum in vivo and in vitro. The present study analyzed the PEA-induced stereotypy and possible associated brain dopamine metabolism in mice. Using male ICR mice treated with a combination of PEA (100 mg/kg, i.p.) and increasing doses of l-deprenyl (0-10 mg/kg, s.c.), we examined (1) the behavioral profile of stereotypy (rating the scores), and (2) the tissue levels of dopamine and its metabolites by high-performance liquid chromatography. The stereotypic scores reached a plateau level at 10 min which lasted until 30 min after a single administration of 100 mg/kg PEA. The stereotyped behavior completely disappeared 45 min after PEA administration. Pretreatment with l-deprenyl (0.1, 1, and 10 mg/kg, s.c.) dose-dependently prolonged the duration of PEA-induced stereotypy. Notably, pretreatment with l-deprenyl dose-dependently increased the continuous sniffing. Treatment with PEA in combination of l-deprenyl (1 and 10 mg/kg) significantly reduced the level of dopamine in the region of the striatum and nucleus accumbens, compared with control animals. These results suggest that PEA in combination with l-deprenyl prolonged the duration of the stereotypy (particularly, continuous sniffing) while reducing the striatal level of dopamine.

Animals↗