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Results for “Stereotyped Behavior”

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PubMed1995

Failure of naltrexone hydrochloride to reduce self-injurious and autistic behavior in mentally retarded adults. Double-blind placebo-controlled studies.

BACKGROUND: It is hypothesized that self-injurious behavior (SIB) and symptoms of autism may be due to overactivity in some opioid systems in the brain. We examined the efficacy and safety of naltrexone hydrochloride, an opioid antagonist, in the treatment of SIB and autism in mentally retarded adults. METHOD: Thirty-three mentally retarded adults with autism and/or SIB participated in double-blind, placebo-controlled crossover studies. Active treatment was first a single 100-mg dose of naltrexone hydrochloride. Subsequently, 19 subjects were treated with 50 mg/d and 14 with 150 mg/d of naltrexone hydrochloride for 4 weeks. The outcome was assessed by means of direct observations (n = 11) and on the basis of scores on a list of target behaviors, the Aberrant Behavior Checklist, and the Clinical Global Impression Scale. RESULTS: Thirty-two subjects (seven with autism, 16 with autism and SIB, and nine with SIB) completed the trial. Naltrexone treatment failed to have therapeutic effects on SIB and autism. On the contrary, naltrexone increased the incidence of stereotypic behavior on the Aberrant Behavior Checklist, and the care staff evaluated the effect of the 50-mg/d treatment as being significantly worse than that of the placebo treatment as measured by the Clinical Global Impression Scale. CONCLUSION: Our findings suggest that naltrexone has no clinical value for a broad group of mentally retarded subjects with SIB and/or autism.

Adolescent↗

PubMed2005

Essential role of D1 but not D2 receptors in methamphetamine-induced impairment of long-term potentiation in hippocampal-prefrontal cortex pathway.

Methamphetamine (MA) abuse induces deficits in cognitive performance that are related to dysfunction of the prefrontal cortex (PFC). The medial portion of the prefrontal cortex (mPFC) in rats that is crucial for cognitive function has been shown to undergo long-term potentiation (LTP) in the projections from the hippocampus. However, no study has been performed to evaluate the influence of MA on synaptic plasticity in the hippocampal-mPFC pathways. In the present experiments, we investigated the effects of repeated MA administration on hippocampal-mPFC LTP, together with MA-induced stereotyped behaviors. Repeated MA administration produced behavioral sensitization and LTP impairment in the hippocampal-mPFC pathways. The MA-induced impairment of hippocampal-mPFC LTP was prevented by the pretreatment of dopamine 1 (D1) but not dopamine 2 (D2) receptor antagonists, while D1 and D2 receptor antagonists attenuated the MA-induced stereotyped behaviors. These findings suggest that D1 receptors are crucial for the MA-induced deterioration of synaptic plasticity in the hippocampal-mPFC circuits. Impairment of LTP associated with D1 receptor dysfunction may underlie cognitive deficits in MA-dependent subjects.

Analysis of Variance↗

PubMed1999

Effects of the NMDA receptor antagonist D-CPPene on extracellular levels of dopamine and dopamine and serotonin metabolites in striatum of kindled and non-kindled rats.

Electrical kindling in rats has previously been shown to cause a hypersensitivity to amphetamine-like behavioral effects of competitive NMDA receptor antagonists such as D,L-(E)-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849), D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 40116), or 3-(2-carboxypiperazine-4-yl)propenyl-1-phosphonate (SDZ EAA 494; D-CPPene). From this observation, it was concluded that kindling-induced epileptogenesis enhances the potential of competitive NMDA receptor antagonists to induce such unwanted adverse effects, predicting that such drugs may induce more severe side effects in epileptic patients than in healthy volunteers, which was confirmed in clinical trials. In the present study, we thought to examine the biochemical basis for the enhanced susceptibility of kindled rats to amphetamine-like behavioral effects of NMDA receptor antagonists by measuring extracellular levels of dopamine, the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin (5-hydroxytryptamine, 5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of awake, behaving rats, using in vivo microdialysis. When administered systemically, D-CPPene, 15 mg/kg i.p., caused more intense stereotyped behaviors in kindled than in non-kindled rats. While there was no significant alteration in extracellular dopamine, in both groups of rats HVA and 5-HIAA significantly increased. In kindled rats, basal levels of HVA and the increase in HVA in response to D-CPPene were higher compared to non-kindled animals. When administered intrastriatally via the microdialysis probe, D-CPPene, 10 microM, significantly increased dopamine, HVA and 5-HIAA, which was associated with stereotyped behaviors. Again, these behaviors were more intense in kindled rats. The data indicate that a competitive NMDA receptor antagonist at high, behaviorally active doses induces increases in striatal dopamine and presumably also 5-HT release, which most likely underlie the amphetamine-like behavioral effects of such a drug. Kindling enhances the sensitivity to these behavioral effects, which could be related to a more marked dopamine and 5-HT release. Thus, in order to avoid false predictions for the clinical situation, it is important to study the behavioral and biochemical effects of NMDA receptor antagonists not only in naive, healthy animals but also in animals that mimic the disease for which a drug is developed.

Amygdala↗

PubMed1984

Electrophysiological, biochemical and behavioral assessment of dopamine autoreceptor activation by a series of dopamine agonists.

The rank order of potency to activate central dopamine autoreceptors of seven compounds known to possess central nervous system dopamine agonist activity were assessed with the following techniques: (1) inhibition of dopaminergic neuronal firing in anesthetized rats, (2) inhibition of dopamine synthesis in rats pretreated with gamma-butyrolactone, and (3) inhibition of mouse locomotor activity. The compounds were also examined for their ability to induce stereotypic behaviors in rats as an index of postsynaptic dopamine receptor activation. The compounds under investigation were apomorphine, N-n-propyl-norapomorphine, lergotrile, bromocriptine, RU 24926 and 6-ethyl-9-oxaergoline (EOE). There was a high degree of correlation between the rank order of potency of the compounds in all three of the presumptive autoreceptor tests and with minor variations the following rank order of potency was found: N-n-propylnorapomorphine greater than or equal to EOE greater than apomorphine greater than lergotrile greater than or equal to RU 24926 greater than bromocriptine. However, in the induction of stereotypies, the rank order of potency was considerably different: N-n-propylnorapomorphine greater than apomorphine greater than EOE greater than RU 24926 greater than lergotrile greater than bromocriptine. There was a poor and statistically significant degree of correlation between the rank order of potency of the test compounds to induce stereotyped behaviors and any of the other three test procedures. Altogether, these data confirm and extend the suspected dopaminergic agonist properties of the compounds under investigation and additionally lend credence to the assumption that the three putative autoreceptor assays employed do in fact reflect dopaminergic autoreceptor activation.

4-Butyrolactone↗

PubMed1989

Effects of mafoprazine, a phenylpiperazine derivative, on the central dopaminergic system.

The effects of mafoprazine, a new phenylpiperazine derivative, on the central dopaminergic system were studied. Mafoprazine, like chlorpromazine and haloperidol, reduced the apomorphine-induced cage-climbing behavior in mice, emesis in dogs and stereotyped behavior in monkeys; methamphetamine-induced hyperlocomotion and group toxicity in mice; and agitation in rats. Mafoprazine inhibited the unilateral circling behavior induced by methamphetamine and apomorphine in rats with 6-hydroxydopamine-induced lesions in the unilateral nigrostriatal neuronal tract. The potency of mafoprazine in these experiments was almost equal to that of chlorpromazine and about one-tenth that of haloperidol. The cataleptogenic activity of mafoprazine was lower than those of chlorpromazine and haloperidol. Mafoprazine potentiated clonidine-induced hypothermia. These results suggest that mafoprazine has a relatively selective postsynaptic dopamine D2-receptor blocking action in the nucleus accumbens compared with chlorpromazine and haloperidol and suggest that mafoprazine also has alpha 2-adrenoceptor-stimulating actions.

Aggression↗

PubMed2006

Effects of activation of D1 dopamine receptors on extinction of a conditioned passive avoidance reflex and amnesia in aggressive and submissive mice.

The studies reported here demonstrate the relationship between the effect of activation of D1 dopamine receptors on the reproduction of a conditioned passive avoidance reflex during extinction and amnesia and the aggressive and submissive behavioral stereotypes. During extinction, the D1 receptor agonist SKF 38393 at a dose of 5 mg/kg given before acquisition of the conditioned reflex and on test day 12 suppressed the reproduction of the conditioned skill in aggressive mice and improved reproduction in submissive mice. The effects of activation of D1 receptors were also opposite relative to the stereotype in amnesia. In aggressive mice, SKF 38393 significantly decreased the resistance to amnesia characteristic of these animals; in submissive mice, SKF 38393 weakened the amnestic effects of the delay in the "dangerous" sector and restored memory traces. The possible mechanisms of the selectivity of the actions of D1 receptors in mice with alternative behavioral stereotypes in retaining memory traces related to aversive stimulation during extinction and amnesia are discussed.

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

PubMed2006

Acute and chronic tianeptine treatments attenuate ethanol withdrawal syndrome in rats.

Effects of acute and chronic tianeptine treatments on ethanol withdrawal syndrome were investigated in rats. Ethanol (7.2% v/v) was given to adult male Wistar rats by a liquid diet for 30 days. Acute or chronic (twice daily) tianeptine (5, 10 and 20 mg/kg) and saline were administered to rats intraperitoneally. Acute and last chronic tianeptine injections and saline were done 30 min before ethanol withdrawal testing. After 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs which included locomotor hyperactivity, agitation, tremor, wet dog shakes, stereotyped behavior and audiogenic seizures were recorded or rated. Locomotor activity in naive (no ethanol-dependent rats) was also tested after acute tianeptine treatments. Acute but not chronic tianeptine treatment attenuated locomotor hyperactivity and agitation in ethanol-dependent rats. Both acute and chronic tianeptine treatment produced some significant inhibitory effects on tremor, wet dog shakes, stereotyped behaviors and audiogenic seizures during the ethanol withdrawal. Our results suggest that acute or chronic tianeptine treatment attenuates ethanol withdrawal syndrome in ethanol-dependent rats and this drug may be useful for treatment of ethanol-type dependence.

Animals↗

PubMed1996

A comparative study of the anorectic and behavioral effects of fenproporex on male and female rats.

The anorectic and behavioral effects of fenproporex (Fenp, 10 mg/kg, ip) and methamphetamine (Met, 2.5 mg/kg, ip), a prototypical example of an amphetamine-like drug, were studied in male and female Wistar rats (5 and 3 months of age, respectively, at the beginning of the experiments) after acute (immediately after a single dose) or chronic treatment (after 60 days of administration). For the evaluation of the experimental parameters six groups of eight rats each were utilized for food intake and stereotyped behavior and six groups of nine rats each for body weight and motor activity. Similar anorectic effects (decreased food intake in grams: saline (Sal): 12.8 +/- 2.5, Met: 4.7 +/- 4.0, and Fenp: 4.4 +/- 20; decreased weight gain: Sal: 38 +/- 10, Met: 25 +/- 1.0, and Fenp: 27 +/- 3.0) were induced by both drugs in male rats. Female rats, however, required larger doses (20 mg/kg Fenp and 5.0 mg/kg Met) for a complete blockade of food intake. The behavioral tests were carried out 30, 60, 120, 180 and 300 min after drug administration and on day 1 and day 60 immediately after the treatment, for stereotypy and motor activity, respectively (male rats: Met: 3.8 +/- 0.3, Fenp: 6.0 +/- 0.9, and female rats: Met: 15.4 +/- 1.9, Fenp: 9.7 +/- 1.3). Though stereotyped behavior such as sniffing, continuous licking, and false bites was observed in all animals, this was more evident and prolonged in female rats. Both drugs also increased motor activity (male rats, acute treatment: Met: 608 +/- 419, Fenp: 677 +/- 354; chronic treatment: Met: 701 +/- 423, Fenp: 908 +/- 479; female rats, acute treatment: Met: 817 +/- 350, Fenp: 1177 +/- 282; chronic treatment: Met: 623 +/- 274, Fenp: 1511 +/- 573) with female rats once again showing greater sensitivity both after acute and chronic treatment. Our data indicate that fenproporex, like methamphetamine, has a stimulating effect on the central nervous system, indicating an action on the dopaminergic systems. These data further suggest that its therapeutic use as an appetite moderator should be prescribed with caution, especially to women, since, at least in the species studied, the female organism seems to show higher susceptibility to the central effects of this substance.

Animals↗

PubMed1976

Behavioral changes in a juvenile primate social colony with chronic administration of d-amphetamine.

Three selected members of a stable juvenile primate social colony of six, peer-raised, one-year old Stumptail macaques received 0.5 mq/kg of d-amphetamine sulfate daily for four weeks. Amphetamine significantly reduced play activity to a minimum in the treated monkeys throughout the treatment period. These animals preferred huddling with eyes open, although no sedation was apparent. As the treatment period progressed, stereotyped behavior developed, rising significantly during the final week of treatment. This model may be useful in studying the seemingly "paradoxical" quietening effect of amphetamine in children.

Amphetamine↗

PubMedDate not supplied

Effects of nitrous oxide exposure on behavioral changes in mice.

This study was designed to examine the effects of continuous exposure to low levels of nitrous oxide on several behavioral paradigms and the occipital cortex cells of mice. Different groups of mice were exposed to air or two different levels of nitrous oxide (1000 ppm or 2000 ppm) 8 hr/day for eight consecutive days. The exposure to nitrous oxide was achieved by placing animals in a specially designed, enclosed chamber. At the end of the exposure period, all mice were tested for motor coordination, locomotor activity, stereotypic behavior and anxiety level. Cellular examination of the occipital cortex was conducted by counting both the larger neural cells and the smaller neuroglial cells in a specific region. Our results indicated that animals showed no deficit in motor coordination or anxiety level. Histological examination indicated no significant difference in the number of neural cells, neuroglial cells, or total cells counted in the control tissue, as compared to the neural tissue from mice exposed to nitrous oxide. Nitrous oxide-exposed mice showed reduced locomotor activity compared to control animals; however, with the exception of one time period, this decrease was not statistically significant. Animals exposed to nitrous oxide showed a dose-dependent reduction in stereotypic behavior. Our results suggest that short-term exposure to trace levels of nitrous oxide might alter central dopaminergic neuronal activities in striatal and mesolimbic regions. Further research in this area is needed to provide more information regarding the potential effects of repeated exposure to low levels of nitrous oxide. (Pediatr Dent 15:93-98, 1993).

Analysis of Variance↗

PubMed1993

[Effects of antagonists of NMDA receptor on methamphetamine-induced decrease in the dopamine uptake sites in the rat striatum and on the behavioral sensitization].

In humans, repeated use of methamphetamine produces hypersensitivity to the psychotogenic effects of methamphetamine that persists for months to years after the discontinuation of methamphetamine administration. Methamphetamine-induced psychosis has been thought to be a useful experimental model for schizophrenia. A possible involvement of the glutamate system in the hypersensitivity including behavioral sensitization or reverse tolerance is recognized in an animal model for methamphetamine psychosis. We investigated the effects of antagonists of N-methyl-D-aspartate (NMDA) receptor on methamphetamine-induced decrease in dopamine (DA) uptake sites in the rat striatum and on the behavioral sensitization. Repeated administrations of escalating doses of methamphetamine (2.5, 5, 7.5, 10mg/kg s. c. x 2, every other day for a week) decreased DA uptake sites to about 75% of the control in the striatum assayed by binding with [3H]GBR 12935. Co-administration of MK-801, a non-competitive antagonist of NMDA receptor, and methamphetamine significantly prevented the methamphetamine-induced decrease in striatal [3H]GBR 12935 binding in a dose dependent manner. Administration of MK-801 alone did not affect the [3H]GBR 12935 binding. Furthermore, co-administration of SDZ EAA494, a competitive antagonist of NMDA receptor, and methamphetamine also prevented the methamphetamine-induced decrease in the striatal [3H]GBR 12935 binding in a dose dependent manner. In methamphetamine-pretreated rats, the methamphetamine challenge (2.5mg/kg) after a 7-day-drug-free period produced an initial elevation in locomotion lasting for 10-30 min which was followed by a precipitous drop in the locomotion activity to very low levels for approximately 50-70 min. During the period of reduced locomotor activity, methamphetamine-pretreated rats showed intense focused stereotyped behavior. In contrast, animals treated with both MK-801 and methamphetamine showed neither the progressive enhancement of the locomotor activity nor the stereotyped behavior induced by the drug. Pretreatment with MK-801 blocked the development of the methamphetamine-induced behavioral sensitization. These results suggest an involvement of excitatory amino acids in neurochemical effects of methamphetamine on the dopamine system in the striatum.

Animals↗

PubMed2006

Modification of morphine-induced hyperlocomotion and antinociception in mice by clorgyline, a monoamine oxidase-A inhibitor.

We evaluated the effects of pretreatment with clorgyline, an irreversible monoamine oxidase (MAO)-A inhibitor, on morphine-induced hyperlocomotion and antinociception. A single administration of morphine (30 mg/kg, i.p.) to male ICR mice induced a hyperlocomotion. ANOVA analysis revealed the statistical significance of the morphine effect on horizontal locomotion and of the clorgyline pretreatment x morphine interaction effect, but not of the effect of clorgyline pretreatment. The initial (5 min after challenge) phase of morphine actions vs. saline challenge appeared as if morphine had a strong inhibitory effect on locomotor activity in combination with different doses of clorgyline. The mice administered with morphine in combination of clorgyline (1 and 10 mg/kg) did not show any stereotypic behaviors. Clorgyline at a dose of 0.1 mg/kg but not other doses tested significantly potentiated morphine-induced antinociception evaluated by tail flick but not hot plate test. During the measurements of locomotor activity and antinociception, clorgyline at doses of 1 and 10 mg/kg significantly inhibited monoamine metabolism through MAO. These results suggest that clorgyline showed an inhibitory effect on morphine-induced hyperlocomotion, but not antinociception, through MAO inhibition. There is not a possibility that clorgyline pretreatment enhanced morphine action on motor activity, resulting in the abnormal behavior from hyperlocomotion to stereotypic movements.

Analgesics↗

PubMed2006

Attenuation of ethanol withdrawal syndrome by extract of Hypericum perforatum in Wistar rats.

The effects of Hypericum perforatum (St John's wort) on ethanol withdrawal syndrome have been investigated in ethanol-dependent rats. Adult male Wistar rats were subjects. Ethanol (7.2% v/v) was given to rats by a liquid diet for 15 days. Hypericum perforatum extract (HPE) (25-200 mg/kg) and saline were injected to rats intraperitoneally just before ethanol withdrawal. After second, fourth and sixth hour of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, stereotyped behavior and tremors were recorded or rated. A second series of injections was given at 6 h after the first one, and subjects were then tested for audiogenic seizures. HPE (25-200 mg/kg) produced some dose-dependent and significant inhibitory effects on locomotor hyperactivity at second and sixth hour of ethanol withdrawal. In addition, it significantly reduced the number of stereotyped behaviors at the same dose range. HPE (50 and 100 mg/kg) produced some significant inhibitory effects on tremor and audiogenic seizures during withdrawal period. These results suggest that HPE has some beneficial effects on ethanol withdrawal syndrome in rats.

Animals↗

PubMed2000

Alterations of conditioned taste aversion after microiontophoretically applied neurotoxins in the medial prefrontal cortex of the rat.

The prefrontal cortex (PFC) has been reported to be essential in neural control of feeding. In the present study, we aimed to provide a complex characterization of behavioral consequences of PFC microlesions in CFY rats. Kainic acid (KA) was microiontophoretically applied into the mediodorsal division of PFC to damage intrinsic neurons, whereas in another group of rats, 6-hydroxydopamine (6-OHDA) was microiontophoretized into the same region to destroy catecholaminergic (CA) projection fiber terminals. Body weights, food and fluid intake of both lesioned and (sham-operated or intact) control animals were daily measured. Effects of intracellular dehydration and water deprivation were also studied. Open field activity, stereotyped behaviors, and orientation towards visual and somesthetic stimuli were pre- and postoperatively tested. To examine hypothesized consequences of mPFC microlesions on central taste information processing, the acquisition and retention of saccharine conditioned taste aversion (CTA) were studied. No major changes were recorded in body weights, food and water consumption. Dehydration or deprivation similarly increased water intake in all animals. Scores of open field activity and stereotyped behaviors in the 6-OHDA group were significantly higher than those of the other groups. As the main findings of the present studies, both KA and 6-OHDA lesioned rats displayed significant deficits in CTA acquisition and retention tests. These results suggest that the medial PFC has a substantial role in both the formation and the retrieval of CTA. Furthermore, the present findings also indicate the general significance of prefrontal CA mechanisms in the organization of goal-directed, adaptive behaviors.

Animals↗

PubMed2000

Motor stimulation following bilateral injection of the group-I metabotropic glutamate receptor agonist into the dorsal striatum of rats: evidence against dependence on ionotropic glutamate receptors.

RATIONALE: Group-I metabotropic glutamate receptors (mGluRs) are densely expressed in the medium-sized spiny projection neurons of the striatum. Activation of the group-I mGluRs in the rat striatum with a selective group-I agonist, 3,5-dihydroxyphenylglycine (DHPG), produced locomotion and stereotypical behavior. OBJECTIVES: This study was designed to evaluate dependence of DHPG-stimulated motor behaviors on the ionotropic glutamate receptors [N-methyl-D-aspartate (NMDA) and kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazoleprionic acid (AMPA)]. METHODS: In chronically cannulated rats, effects on motor activity of DHPG injected into the dorsal striatum were examined in the presence or absence of the antagonists selective for NMDA or kainate/AMPA receptors. RESULTS: Bilateral injections of DHPG (80 nmol) into the dorsal striatum induced a delayed locomotion followed by a prolonged stereotypical behavior characterized by the repetitive twitching movement of the head and forepaws. Blockade of NMDA receptors with intrastriatal injection of the NMDA receptor antagonist, (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 2.5 nmol), did not attenuate the behavioral changes induced by DHPG administration. Conversely, CPP unmasked an early onset of locomotion in response to DHPG injection as opposed to the delayed locomotion induced by DHPG in the absence of CPP. Pretreatment of rats with the kainate/AMPA receptor antagonist, 6,7-dinitroquinoxaline2,3-dione (DNQX, 10 nmol), had no effect on DHPG-stimulated behaviors. CPP administered alone sedated animals, whereas DNQX given alone did not alter spontaneous behavioral activity. CONCLUSIONS: Motor stimulation induced by activation of the DHPG-sensitive group-I mGluRs in the striatum is independent upon co-activation of NMDA or kainate/AMPA receptors, since the NMDA or the kainate/AMPA receptor antagonist had no effect on DHPG-stimulated motor activity.

Animals↗

PubMed2001

Autism in tuberous sclerosis complex is related to both cortical and subcortical dysfunction.

OBJECTIVE: To examine the relationship between autism and epilepsy in relation to structural and functional brain abnormalities in children with tuberous sclerosis complex (TSC). METHODS: Children with TSC and intractable epilepsy underwent MRI as well as PET scans with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and alpha-[(11)C]methyl-L-tryptophan (AMT). Based on the results of Autism Diagnostic Interview-Revised, Gilliam Autism Rating Scale, and overall adaptive behavioral composite (OABC) from Vineland Adaptive Behavior Scale, subjects were divided into three groups: autistic (OABC < 70; n = 9), mentally-retarded nonautistic (OABC < 70; n = 9), and relatively normal intelligence (OABC > or = 70; n = 8). RESULTS: PET studies showed that the autistic group had decreased glucose metabolism in the lateral temporal gyri bilaterally, increased glucose metabolism in the deep cerebellar nuclei bilaterally, and increased AMT uptake in the caudate nuclei bilaterally, compared to the mentally-retarded nonautistic group. In addition, a history of infantile spasms and glucose hypometabolism in the lateral temporal gyri were both significantly associated with communication disturbance. Glucose hypermetabolism in the deep cerebellar nuclei and increased AMT uptake in the caudate nuclei were both related to stereotypical behaviors and impaired social interaction, as well as communication disturbance. CONCLUSIONS: These results suggest that generalized epilepsy in early life and functional deficits in the temporal neocortices may be associated with communication delays, and that functional imbalance in subcortical circuits may be associated with stereotypical behaviors and impaired social interaction in children with TSC.

Adolescent↗

PubMedDate not supplied

Receptor subtype-specific dopaminergic agents and unconditioned behavior.

When all of the data concerning the role of D1 and D2 receptors in the control of unconditioned behaviors are taken together a fairly consistent picture begins to emerge. Considering first the normosensitive animals, it appears that D1 and D2 receptors are interdependent in their involvement in the control of locomotor activity. Stimulation of either receptor subtype leads to increases in activity although D2 agonists generally have a larger effect on activity than D1 agonists. Subeffective doses of D1 and D2 agonists (or D1 and D2 antagonists) have a synergistic action when co-administered. Injections of antagonists specific for either receptor subtype leads to a decrease in unstimulated locomotor activity or a diminution in the effects of agonists stimulating either receptor subtype. Besides locomotor activity, stimulation of D2 receptors produces yawning but a consistent effect on grooming has not been seen; D2 receptor stimulation also produces stereotyped behaviors. Again, there seems to be an interdependence between the two receptor subtypes; yawning or stereotypy produced by D2 receptor stimulation is blocked by either D2 or D1 antagonists. Stimulation of D1 receptors produces grooming and small perioral movements but not stereotyped behaviors like those typically seen following large doses of D2 agonists or DA agonists not specific a receptor subtype. Unlike D1 receptor-stimulated locomotor activity which is antagonized by D2 receptor blockers, grooming and perioral movements are not (but see Ref. 81). Thus, D1 receptor-mediated grooming and perioral movements seem to be exceptions to the otherwise general finding that co-stimulation of the two receptor subtypes needed for the expression of D1 or D2 agonist effects in normosensitive rats and mice. The apparent need to stimulate both D1 and D2 receptors to produce locomotor and some other unconditioned behaviors in normosensitive animals is lost in chronically denervated animals that are supersensitive to the effects of DA or DA agonists. However, there appear to be important species differences. Generally, in rodents undergoing unilateral or bilateral 6-OHDA-induced destruction of the nigrostriatal DA system, the locomotor effects of D1 agonists are not blocked by D2 antagonists and those of D2 agonists are not blocked by D1 antagonists. Similar results have been reported following chronic treatments with catecholamine depleting drugs. Thus, stimulation of either D1 or D2 receptors alone in DA supersensitive rodents appears to be sufficient to produce locomotor activity. In primates made DA supersensitive either with MPTP or as a result of Parkinson's disease, on the other hand, D2 but not D1 agonists are effective in reversing locomotor deficits.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2001

Seizure activity and hyperthermia potentiate the increases in dopamine and serotonin extracellular levels in the amygdala during exposure to d-amphetamine.

Behavioral stereotypy, hyperthermia, and convulsive activity produced by exposure to multiple doses of d-amphetamine (AMPH) were related to changes in the extracellular levels of dopamine and serotonin (5-HT) in the amygdala, using the technique of microdialysis in awake and freely moving rats. Hyperactivity and stereotypy, as well as increases in microdialysis dopamine levels ranging from 100-300% of pre-AMPH basal microdialysate levels (BL), occurred during exposure to 3 doses of 2.5 mg/kg (3 x 2.5 mg/kg) AMPH. Three doses of 5 mg/kg produced a more intense stereotypic behavior as well as hyperthermia, and resulted in large increases in the peak dopamine levels (700% BL) while 5-HT levels were increased to a lesser extent (300% BL). The highest doses tested of 3 x 15 mg/kg produced convulsive activity, seizures, intense stereotypy and hyperthermia with peak microdialysate dopamine (1300% BL) and 5-HT levels (1800% BL) that were 2-fold and 6-fold greater, respectively, than those at the 3 x 5-mg/kg doses. Microdialysate glutamate levels were not changed by AMPH exposure. Rats that did not become hyperthermic when dosed with 15 mg/kg AMPH in a cold environment (10 degrees C) exhibited some hyperactivity and stereotypic behavior, but not overt convulsive behavior. Dopamine and 5-HT levels in these rats were significantly reduced by about 75% and 60%, respectively, compared to the room-temperature group. Inclusion of 2 microM tetrodotoxin (TTX) in the microdialysis buffer significantly reduced the 15-mg/kg AMPH-induced increases in dopamine by 30% and the increase in 5-HT levels by 70% at room temperature. These results indicate that a smaller portion of the dopamine release evoked by doses of AMPH that induce seizure activity is neuronal impulse-dependent while the majority of 5-HT released is impulse-dependent. Irrespective of impulse activity, the hyperthermia alone markedly potentiated dopamine release but had a lesser effect on 5-HT release. Thus, there are differences in the regulation of dopamine and serotonin release in the amygdala from high doses of AMPH, which are known to produce neurotoxicity. Further studies are necessary to determine the impact of these differences in release on AMPH neurotoxicity.

3,4-Dihydroxyphenylacetic Acid↗