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Effect of methylphenidate pretreatment on the behavioral and biochemical responses to amphetamine.

After rats were chronically pretreated with methylphenidate (MP), the stereotyped behavioral response to amphetamine (AMPH) was significantly enhanced. In addition, after this pretreatment, the AMPH-induced release of endogenous dopamine from slices of striatum and nucleus accumbens was also enhanced. These effects of MP pretreatment are similar to those reported for AMPH pretreatment and suggest that the sensitization to AMPH that develops after pretreatment with either drug is due to a common mechanism.

Amphetamine↗

Dexamethasone modifies the behavioral effects induced by clonidine in mice.

The present study examines the influence of dexamethasone on behavioral effects induced by clonidine in mice. 2. The behavior elements considered were locomoter activity, rota rod, catalepsy and stereotyped behavior (rearing, grooming, social response test, crossing, smelling, washing face, scratching and bar holding). 3. Clonidine (0.1-0.5-1.0 mg/kg, IP) induced a significant reduction of all behavioral elements studied when compared to the saline treated group: the behavioral reduction was significant 10 min after administration and lasted for the entire recording period (120 min). 4. Dexamethasone (0.1-0.5-1.0 mg/kg, IP) per se did not induce significant changes in the behavior elements recorded. 5. Dexamethasone (0.1-0.5 mg/kg, IP) dod not affect behavioral effects induced by the 3 doses of clonidine, whereas the high dose (1 mg/kg) of the steroid significantly reduced its behavioral inhibition. 6. The results of the present study suggest that dexamethasone induces significant effects on clonidine-induced behavioral effects and that this may be related to an interference with the monoaminergic system.

Animals↗

Cortical administration of somatostatin (SRIF): effect on sleep and motor behavior.

Cortical administration of SRIF in unrestrained, freely moving rats produced an early activation, stereotyped behavior patterns and later, coordination difficulties often associated with drowsiness. A few animals showed a tendency toward paraplegia-in-extension. A considerable, prolonged alteration in the sleep-waking cycle was also observed. Similar results were obtained in both intact and hypophysectomized animals. Intraperitoneal administration of SRIF induced several other effects in addition to those seen after cortical application. The latter were however, restricted in variety, intensity and duration.

Animals↗

The comparative long-term effects of ciladopa (AY-27,110), a chemically novel dopaminergic agonist, in 6-OHDA-lesioned and intact rats.

The effect of the chemically novel dopaminergic agonist, ciladopa (AY-27,110) was studied on rotational behavior in unilaterally 6-OHDA-lesioned rats and on stereotyped behavior in normal animals during and after chronic treatment. Ciladopa, at a 1.25 mg/kg SC daily dose, was administered for 4 and 6 weeks to the lesioned and normal animals, respectively. This dose was threshold for turning but subthreshold with respect to stereotypy. Both behaviors were evaluated weekly during chronic treatment and biweekly for 11 weeks after its discontinuation in response to doses previously shown to elicit turning and stereotypy. The chronic administration of ciladopa enhanced rotational behavior considerably more and with an earlier onset than stereotypy, although the duration of behavioral supersensitivity after cessation of treatment was the same. These results indicate that behaviors mediated by supersensitive or intact dopamine receptors are differently affected by chronic dopamine agonist treatment. The results are discussed in relation to their potential therapeutic implications and current concepts of agonist-induced supersensitivity.

Animals↗

Central 5-HT(4) receptors and dopamine-dependent motor behaviors: searching for a functional role.

In this study, we evaluated the role of central 5-HT(4) receptors in the control of motor behaviors related to change of nigrostriatal dopamine (DA) transmission, namely, stereotyped behavior and catalepsy in rats. Indeed, given that 5-HT(4) receptors indirectly modulate nigrostriatal DA neuron activity, we hypothesized that these receptors would regulate nigrostriatal DA transmission in the basal ganglia, and consequently, associated motor responses. Stereotypy was induced either by an acute administration of apomorphine (0.3 and 1.5 mg/kg sc), or by a single morphine administration (15 mg/kg sc) in chronically morphine-treated (15 mg/kg sc, twice daily for 10 days) rats. Catalepsy was induced by the typical neuroleptic haloperidol (HAL; 1 mg/kg sc). The selective 5-HT(4) antagonist, GR 125487 (1 mg/kg ip), modified neither apomorphine- nor morphine-induced stereotypy. HAL-induced catalepsy, while reduced by the systemic administration of the 5-HT(1A) agonist 8-OH-DPAT (0.1 mg/kg sc), was insensitive to GR 125487, systemically (1, 3, 10 mg/kg ip) or locally (20 and 40 nmol/20 microl) administered into the third ventricle. Also, HAL-induced catalepsy was not affected by the selective 5-HT(4) antagonist GR 113808 (3 mg/kg ip). The obtained results indicate that 5-HT(4) receptor antagonism does not modulate motor behaviors related to change of striatal DA transmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Convergent validity of the aberrant behavior checklist and behavior problems inventory with people with complex needs.

The current study aimed to replicate and extend Rojahn et al. [Rojahn, J., Aman, M. G., Matson, J. L., & Mayville, E. (2003). The aberrant behavior checklist and the behavior problems inventory: Convergent and divergent validity. Research in Developmental Disabilities, 24, 391-404] by examining the convergent validity of the behavior problems inventory (BPI) and the aberrant behavior checklist (ABC) for individuals presenting with multiple complex behavior problems. Data were collected from 69 children and adults with severe intellectual disabilities and challenging behavior living in residential establishments. MANCOVA analyses showed that individuals with elevated BPI stereotyped behavior subscale scores had higher scores on ABC lethargy and stereotypy subscales, while those with elevated BPI aggressive/destructive behavior subscale scores obtained higher scores on ABC irritability, stereotypy and hyperactivity subscales. Multiple regression analyses showed a corresponding pattern of results in the prediction of ABC subscale scores by BPI subscale scores. Exploratory factor analysis of the BPI data suggested a six-factor solution with an aggressive/destructive behavior factor, four factors relating to stereotypy, and one related to stereotypy and self-injury. These results, discussed with reference to Rojahn et al. [Rojahn, J., Aman, M. G., Matson, J. L., & Mayville, E. (2003). The aberrant behavior checklist and the behavior problems inventory: Convergent and divergent validity. Research in Developmental Disabilities, 24, 391-404], support the existence of relationships between specific subscales of the two instruments in addition to an overall association between total scores related to general severity of behavioral disturbance.

Adolescent↗

Stimulation of presynaptic dopamine autoreceptors by 4-(2-di-n-propylaminoethyl) indole (DPAI).

The dopaminergic activity of 4-(2-di-n-propylaminoethyl)indole (DPAI) was investigated. In animal models for postsynaptic dopaminergic activity DPAI showed only very weak or no effects. In rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal tract, very weak contralateral turning behavior was induced in 4/6 rats. DPAI did not induce stereotyped behavior but caused a pronounced reduction in locomotor activity. In male rats pretreated with reserpine, DPAI lowered serum prolactin levels. Levels of homovanillic acid (HVA) were monitored in the striatum of the chloral hydrate anesthetized rat by means of in vivo voltammetry. DPAI administration reduced the faradaic peak corresponding to HVA. In rats pretreated with the decarboxylase inhibitor, NSD-1015, DPAI blocked the accumulation of dopa in response to gamma-butyrolactone. The results of this study indicate that DPAI possesses a high degree of selectivity for presynaptic dopamine autoreceptors, and little or no effect on postsynaptic dopamine receptors.

Animals↗

An organic selenium compound attenuates apomorphine-induced stereotypy in mice.

Selenium compounds display neuroprotective activities mediated at least in part by their antioxidant actions. Oxidative damage has been implicated in psychiatric disorders including schizophrenia and bipolar disorder, and an alteration in expression of selenium-binding protein-1 (SELENBP-1) has been recently reported in both the blood and brain of schizophrenic patients. In the present study we examined the effects of the organic selenium compound 3'3-ditrifluoromethyldiphenyl diselenide [(F3CPhSe)2] on apomorphine-induced stereotypy in mice, an animal model of psychosis. Systemic administration of (F3CPhSe)2 at the highest dose used (25.0 micromol/kg in a 10.0 ml/kg injection volume) significantly reduced apomorphine-induced stereotyped behaviors. A series of control experiments showed that the same dose of (F3CPhSe)2 did not affect open-field behavior, habituation, or aversively motivated memory. The results indicate that organic selenium compounds should be further investigated as agents with possible antipsychotic properties.

Analysis of Variance↗

Effect of daily dose of chronic haloperidol and chronic apomorphine on behavioral hypersensitivity in the rat.

Behavioral hypersensitivity in the rat consisting of increased dopamine-mediated stereotypic behaviors has been found to follow a 10-day course of treatment with the neuroleptic haloperidol as well as with the direct dopamine agonist apomorphine. The daily dose versus response relationship for chronic haloperidol indicates that a threshold daily dose exists and that behaviors increase with increasing daily dose. On the other hand, low rather than high daily doses of chronic apomorphine induce behavioral hypersensitivity and the response decreases with increasing daily dose. Prolonged functional denervation of striatal postsynaptic dopamine receptors by either neuroleptic blockade or autoreceptor stimulation may explain these findings. The results may help elucidate the relative risk of daily neuroleptic dose on tardive dyskinesia development and indicate a possible mechanism for chronic agonist-associated side effects like L-Dopa dyskinesias.

Animals↗

Effect of manipulation of the GABA system on dopamine-related behaviors.

The interaction between GABAergic and dopaminergic systems within the central nervous system was investigated in rats using the open-field apparatus and apomorphine-induced stereotypy, and in mice using haloperidol-induced catalepsy. The single intraperitoneal administration of baclofen 3.0 mg/kg, 4,5,6,7-tetrahydroisoxasolo-(5,4-c) piridin-3-ol (THIP) 10.0 mg/kg and picrotoxin 2.0 mg/kg decreased both ambulation and rearing frequencies of the rats in the open-field; only the GABA agonists increased the duration of animal immobility. THIP (10.0 mg/kg) increased the duration of haloperidol-induced catalepsy. For apomorphine-induced stereotypy, baclofen 3.0 mg/kg and picrotoxin 1.0 mg/kg induced a significant leftward displacement of the control dose-response curve constructed for apomorphine (0.1-10 mg/kg) in relation to the control. In addition, baclofen, THIP, picrotoxin and 3-mercaptopropionic acid (3-MPA) 10.0 mg/kg decreased both rearing and sniffing behaviors elicited by apomorphine and increased licking and/or gnawing. Different mechanisms seem to be involved in the similar effects induced by GABA agonists and antagonists. Picrotoxin induced stereotyped movements per se with a dose-dependent effect, but baclofen and THIP did not. The present data suggest that GABA manipulation facilitates the progressive activation of the different dopaminergic pathways involved in stereotyped behaviors, thus increasing those stereotyped components (gnawing and licking) that appear after a high level of activation of dopaminergic pathways.

3-Mercaptopropionic Acid↗

Reducing self-stimulatory behavior of mentally retarded persons by alternative positive practice.

Wheelchair-mobility training (contingent upon inappropriate stereotypic behavior) combined with social praise (contingent upon toy-play behavior) effectively reduced the inappropriate behavior of three nonambulatory, profoundly retarded subjects to near-zero level. In a multiple-baseline design across subjects, self-directed and outward-directed behavior was recorded in 10-second, continuous intervals during two, 10-minute sessions per day for each subject. Baseline self-directed activity means and outward-directed activity means were altered significantly by the combined treatment approach, an effect confirmed by follow-up data.

Adolescent↗

Toward an empirical method for identifying matched stimulation for automatically reinforced behavior: a preliminary investigation.

The effects of noncontingent matched stimulation (NMS) and response blocking on a boy's stereotypic behavior were evaluated using a multiple schedule that contained three 15-min components (preintervention, intervention, and postintervention). Results showed that stereotypy was always higher after response blocking than before response blocking and was always lower after NMS than before NMS. These results suggest that response blocking may have produced deprivation for the product of stereotypy and that NMS may have provided stimulation that was similar to the product of stereotypy.

Automatism↗

Oligodeoxynucleotide antisense to the D1 dopamine receptor mRNA inhibits D1 dopamine receptor-mediated behaviors in normal mice and in mice lesioned with 6-hydroxydopamine.

The effects of intracerebroventricular (i.c.v.) administration of a 20-mer phosphorothioate oligodeoxynucleotide antisense to the D1 dopamine receptor mRNA (D1 antisense) on D1 dopamine receptor-mediated behaviors were studied in normal mice and in mice with unilateral 6-hydroxydopamine-induced lesions of corpus striatum. Treating mice with D1 antisense inhibited grooming behavior induced by the D1 dopamine receptor agonist SKF 38393 [1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine-7,8-diol hydrochloride], the reduction in grooming being related to the amount and length of time D1 antisense was given, with significant reductions in grooming behavior observed within 2 days of repeated injections of D1 antisense. Administering D1 antisense also inhibited rotational behavior induced by SKF 38393 in mice with unilateral 6-hydroxydopamine-induced lesions of corpus striatum. This inhibitory effect on rotational behavior could not be overcome by increasing the dose of SKF 38393. Recovery from inhibition of both grooming and rotational behaviors occurred after cessation of D1 antisense treatment. An oligomer with a similar composition of bases but placed in a random sequence failed to alter grooming or rotational behaviors induced by SKF 38393. In contrast to its effects on D1-mediated behaviors, treatment with D1 antisense had no significant inhibitory effect on stereotyped behavior induced by the D2 dopamine receptor agonist quinpirole [trans-(-)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H(or 2H)-pyrazolo- (3,4g)-quinoline dihydrochloride] in normal mice and produced no significant inhibition of rotational behavior induced either by quinpirole or by the muscarinic cholinergic agonist oxotremorine in 6-hydroxydopamine-lesioned mice.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology.

OBJECTIVE: Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). The authors report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior. METHOD: The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children's Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales. RESULTS: Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual reactions (subscale III), and sensory responses (subscale IV). No statistically significant difference was observed, however, on the subscale for social relatedness (subscale II) or language (subscale V). Risperidone also resulted in significantly greater reductions in scores on the Children's Yale-Brown Obsessive Compulsive Scale and Vineland maladaptive behavior domain. This pattern of treatment response was maintained for 6 months. CONCLUSIONS: Risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication. Further research is necessary to develop effective treatments for the core social and communicative impairments of autism.

Adolescent↗

Effects of cannabidiol in animal models predictive of antipsychotic activity.

The effects of cannabidiol (CBD) were compared to those produced by haloperidol in rats submitted to experimental models predictive of antipsychotic activity. Several doses of CBD (15-480 mg/kg) and haloperidol (0.062-1.0 mg/kg) were tested in each model. First, CBD increased the effective doses 50% (or) ED50 of apomorphine for induction of the sniffing and biting stereotyped behaviors. In addition, both CBD and haloperidol reduced the occurrence of stereotyped biting induced by apomorphine (6.4 mg/kg), increased plasma prolactin levels and produced palpebral ptosis, as compared to control solutions. However, CBD did not induce catalepsy even at the highest doses, in contrast to haloperidol. Such a pharmacological profile is compatible with that of an "atypical" antipsychotic agent, though the mechanism of action is uncertain and may not be identical to that of the dopamine antagonists.

Animals↗

Analysis of ionic conductance mechanisms in motor cells mediating inking behavior in Aplysia californica.

1. The release of ink in response to a noxious stimulus is a relatively stereotyped behavior produced by strong and long-lasting stimuli. The purpose of this series of papers is to determine the quantitative extent to which the known voltage- and time-dependent ionic conductance mechanisms and synaptic influences can account for the ink gland motor neurons' firing pattern and, thus, the features of the behavior. 2. Four voltage- and time-dependent ionic currents have been analyzed. These include a fast transiet Na+-mediated inward current, a slower Ca2+-mediated inward current, a fast transient K+-mediated outward current, and a slower delayed outward current also mediated by K+ ions. 3. The current-voltage (I-V) relationships, equilibrium potentials, and steady-state activation and inactivation characteristics appear qualitatively similar to comparable currents observed in other gastropod neurons. 4. The recovery from inactivation of the delayed outward current has two time constants, one comparable to the inactivation time constant and the other more than an order of magnitude larger. The fast transient K+ current also appears to have a similar slow recovery from inactivation. 5. The synaptic current contributing to the firing pattern of the ink motor cells is a complex function of time. Initially, the synaptic conductance is high and the equilibrium potential near 0 mV. But, with time there is a gradual decrease in synaptic conductance and shift in the equilibrium potential to more depolarized levels.

Animals↗

Effects of naloxone, metenkephalin, and morphine on phencyclidine-induced behavior in the rat.

The effects of naloxone, metenkephalin, and morphine were tested on phencyclidine(PCP)-induced stereotyped behaviors, ataxia, and hyperactivity in the rat. Naloxone (8 mg/kg) significantly decreased stereotypy, ataxia, and hyperactivity across all PCP doses tested (2.0, 4.0, and 6.0 mg/kg). Metenkephalin (40 micrograms/kg) and morphine (5 and 10 mg/kg) increased ataxia at the 4.0 and 6.0 mg/kg PCP doses. Stereotypy was altered by the opiates in a dose-dependent manner; enhanced by metenkephalin (40 micrograms/kg) at 2.0 mg/kg and inhibited by metenkephalin (40 micrograms/kg) and morphine (10 mg/kg) at 4.0 and 6.0 mg/kg PCP. Locomotor activity was increased by morphine (5 mg/kg) at 2 mg/kg PCP. These results suggest an involvement of central opiate receptor mechanisms in the mediation of PCP-induced behaviors in the rat.

Animals↗