Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Stereotyped Behavior”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 991 records · Page 55Linked to original sources
PubMed1997

Potential antidepressant effects of novel tropane compounds, selective for serotonin or dopamine transporters.

The forced swimming test (FST) predicts the efficacy of clinically effective antidepressants. In the present study, using the FST we examined the antidepressant potential of three novel tropane analogs: 8-methyl-2beta-propanoyl-3beta-(4-(1-methylethyl)phenyl)-8-azabicy clo[3.2.1] (WF-31) and 2beta-propanoyl-3beta-(4-(1-methylethyl)phenyl)-8-azabicyclo[3.2.1 ]octane (WF-50), selective inhibitors of serotonin uptake, and 8-methyl-2beta-propanoyl-3beta-(4-(1-methylphenyl)-8-azabicyclo[3. 2.1] octane (PTT, WF-11), a selective inhibitor of dopamine uptake. Fluoxetine and GBR 12909 were used as controls for selective inhibitors of serotonin and dopamine, respectively. Drugs were administered three times in a 24-hr period between pretest and test sessions. Intraperitoneal administration of WF-31 (0.1-10.0 mg/kg), WF-50 (0.3-10.0 mg/kg) and fluoxetine (0.3-10.0 mg/kg) dose-dependently decreased immobility while increasing swimming. In contrast, WF-11 (0.3-3.0 mg/kg) dose-dependently decreased immobility and increased both swimming and climbing, whereas GBR 12909 (3.0-30.0 mg/kg) decreased immobility, increased climbing but did not affect swimming. In a separate experiment, WF-11 (1.0 mg/kg) increased locomotor activity, whereas a higher dose of WF-11 (3.0 mg/kg) and GBR-12909 (30.0 mg/kg) produced stereotypic behaviors, suggesting that the effects in the FST may have been attributable to increases in general activity. However, the effects of WF-11 on swimming in the FST indicate that WF-11 produces antidepressant-like effects in addition to motor stimulation. These results confirm previous results that behavioral patterns manifested in the FST are characteristic of specific monoamine uptake inhibitors. In addition, these results demonstrate that WF-31 and WF-50 produce behavioral patterns similar to fluoxetine in the FST without accompanying decreases in motor activity, suggesting a potential antidepressant action. Based on comparisons with fluoxetine, the data suggest WF-31 and WF-50 may be therapeutically useful as potential antidepressant medications.

Animals↗
PubMed1989

Preclinical studies on quinelorane, a potent and highly selective D2-dopaminergic agonist.

Quinelorane (LY163502) has the endocrine, neurochemical and behavioral profile of a potent and highly selective D2-dopaminergic agonist. The administration of quinelorane produced dose-related decreases in serum prolactin concentration of reserpinized, male rats and increases in serum corticosterone concentration of male rats. The minimum effective doses (MED) for these effects were 10 and 30 micrograms/kg i.p., respectively. Quinelorane induced increases in 3-methoxy-4-hydroxyphenylglycol-sulfate levels in the brain stem (MED, 30 micrograms/kg i.p.) and decreases in hypothalamic epinephrine levels (MED, 100 micrograms/kg i.p.) in male rats as determined by high-pressure liquid chromatography with electrochemical detection methods. Quinelorane induced increases in extracellular ascorbic acid as determined by in vivo voltammetry in the nucleus accumbens and striatum of male rats. Quinelorane produced concentration-dependent suppression of K+-evoked release of acetylcholine from superfused caudate slices, with an IC50 of approximately 10(-8)M. Quinelorane administration produced dose-related increases in compulsive, contralateral turning in male rats with unilateral nigrostriatal lesions and increases in locomotor activity and stereotypic behavior in male rats. In dogs, quinelorane administration produced dose-related increases in emetic response with an ED50 of 7 micrograms/kg i.v. Quinelorane administration also produced dose-related decreases in the striatal concentrations of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic (MED, 1 microgram/kg i.p. for both metabolites) as determined by high-pressure liquid chromatography with electrochemical detection methods and decreases in extracellular concentrations of homovanillic acid in the nucleus accumbens and striatum as determined by in vivo voltammetry., Quinelorane produced concentration-dependent decreases in K+-evoked dopamine release from superfused striatal slices (IC50 = 3 X 10(-9) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMedDate not supplied

[Selective effect of morphine and diazepam on aggressiveness caused by prolonged administration of apomorphine to rats].

In experiments on rats administration of apomorphine (0.5 mg/kg twice a day for 14 days) caused the intensification of aggressiveness. This exerted no substantial effect on stereotyped behavior. Haloperidol produced inhibitory effect both on aggressiveness and stereotypy. The GABA derivative phenybut did not change the effects of apomorphine. Administration of morphine and diazepam produced a selective inhibition of aggressiveness. In doses exerting antiaggressive effect these substances produced no substantial effect on stereotypy. This antiaggressive effect of morphine and diazepam was suppressed by nalorphine. It is suggested that the endogenous opiate system of the CNS participates in the development of the apomorphine-induced aggressiveness.

Aggression↗
PubMed1980

Oral bioavailability of apomorphine in the rat with a portacaval venous anastomosis.

Orally administered apomorphine failed to produce stereotyped behavior in sham-operated rats, but did so following portacaval venous anastomosis. Brain and serum levels of apomorphine were highly correlated and corresponded with ratings of stereotypy. Tissue levels were undetectable after oral administration of apomorphine in intact rats but in shunted rats, were similar to those found after s.c. injection. These results suggest that a strong first-pass hepatic metabolism may account for the low oral bioavailability of catechol-aporphines.

Administration, Oral↗
PubMed1991

Effects of prenatal diphenhydramine exposure on dopaminergic function in adult rats.

Female pregnant rats were treated with 20.0 mg/kg diphenhydramine (DPH) or the same volume of saline solution (NaCl 0.9%), SC, daily during pregnancy. As adults, male pups were tested for stereotyped behavior in response to apomorphine (1 mg/kg, SC) administration. No differences between DPH-exposed and control rats were evident. In another group of rats, dopamine (DA) and homovanillic acid (HVA) levels were quantified in striatal samples. DA levels were equivalent, but increased levels of HVA were observed. Based upon these data we suggest that prenatal exposure to DPH, a histamine (H1) receptor antagonist, reduces presynaptic dopaminergic mechanisms without altering postsynaptic dopaminergic function in adulthood.

Animals↗
PubMed1982

Synthesis and dopaminergic properties of some exo- and endo-2-aminobenzonorbornenes designed as rigid analogue of dopamine.

Stereospecific syntheses of exo-2-amino-5,6-dihydroxybenzonorbornene (11f), exo-2-amino-6,7-dihydroxybenzonorbornene (11h), exo-2-amino-7,8-dihydroxybenzonorbornene (11g), and endo-2-amino-6,7-dihydroxybenzonorbornene (14d), rigid analogues of dopamine, are described. Compounds 11 h and 14d, their N-methyl (11i and 11j) and N,N-dimethyl (14i and 14j) derivatives, and compounds 11f and 11g were inactive as dopamine agonists when evaluated for dopaminergic activity by their ability to induce stereotyped behavior in mice after subcutaneous injection and by their ability to cause hyperactivity in rats after bilateral injection into the nucleus accumbens. However, compounds 11f, 11g, 11h, and the N-methyl derivatives 11i and 14d were all effective in displacing [3H]-2-amino-6,7-dihydroxytetralin ([3H]ADTN) and [3h[-N-n-propylnorapomorphine ([3H]NPA) from rat striatal membranes.

Animals↗
PubMed1985

Hypothesis: bromocriptine lacks intrinsic dopamine receptor stimulating properties.

Bromocriptine (BRC) produced neither locomotor stimulation nor stereotyped behavior in mice and rats pretreated with reserpine plus alpha-methyl-p-tyrosine (AMPT). However, the blockade of locomotor stimulation in mice by AMPT could be reversed by their prior treatment with a low, behaviorally inactive dose of L-DOPA. BRC potentiated the stereotypy (rats) and locomotor stimulation (mice) produced by apomorphine in animals pretreated with reserpine plus AMPT. Moreover, BRC potentiated the stimulant effect of d-amphetamine in reserpinized mice, while nomifensine, but not fluoxetine or desipramine, potentiated the stimulant effect of BRC in mice. After direct application to the nucleus accumbens or caudate nucleus of rats, BRC was inactive. However, when BRC and DA were applied together to the nucleus accumbens, BRC enhanced the stimulant effect of DA. These data show that BRC by itself does not cause behavioral stimulation in rodents. Despite having affinity for the DAD 2-receptor, BRC is incapable of causing excitation in rats and mice unless another DA-receptor agonist such as apomorphine or DA is present. The data are discussed in relation to the published literature and the hypothesis presented that BRC affects the signal transmitted by DA-receptor agonists such as apomorphine at or beyond the postsynaptic DA-receptor.

Adenylyl Cyclases↗
PubMedDate not supplied

Functional and dispositional tolerance develops during continuous cocaine exposure.

Despite the fact that high doses of cocaine are abused chronically, relatively little is known regarding the development of tolerance and/or sensitization under these circumstances. Therefore, male Sprague-Dawley rats were infused continuously i.v. for 10 days, at a rate of 150 mg/kg/day (0.1 mg/kg/min) with cocaine hydrochloride. Body weight, food and water consumption, urine and fecal excretion, as well as blood pressure, heart rate and stereotypic behavior were monitored daily. Blood samples were also drawn daily so that plasma could be analyzed for cocaine and BEG by gas chromatography/mass spectrometry. Severe body weight loss on days 1 through 4 was followed by a gradual return to pre-drug levels. In addition, cocaine's effects on food and water consumption and urine and fecal excretion, which were maximal by day 2, were imperceptible by day 5. Complete tolerance developed rapidly to the remarkable rise in blood pressure noted on the first day. However, tolerance did not develop to the cocaine-induced increase in heart rate. A profound decrease in heart rate was noted in some animals which was interpreted to be cardiotoxicity since these animals subsequently died. On the other hand, sensitization or intensification of behavioral stereotypy occurred during the first 2 days followed by complete tolerance to this effect by day 5. No withdrawal phenomena were noted 24 h after cocaine was abruptly withdrawn. Plasma concentrations of cocaine rose rapidly during the first day and remained elevated at a constant level until day 5. Then, a sharp decline in plasma levels occurred at day 6 which remained depressed for the duration of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

On the mechanism which mediates the effects of long-term administration of fencamfamine in rats.

This study analyzes the changes in the sensitivity of striatal dopaminergic (DA) receptors to apomorphine following withdrawal from long-term treatment with fencamfamine (10 mg/kg, for 40 days). Fencamfamine treatment decreased (34.8 +/- 3.2 vs 25.8 +/- 2.8, P less than 0.05) the stereotyped behavior induced by apomorphine (2.0 mg/kg, sc), but potentiated the effect of apomorphine (0.02 mg/kg, sc) in reducing the striatal levels of homovanillic acid (HVA) (0.41 +/- 0.02 micrograms/g vs 0.31 +/- 0.03 micrograms/g, P less than 0.01) and dihydroxyphenylacetic acid (DOPAC) (0.45 +/- 0.04 micrograms/g vs 0.34 +/- 0.03 micrograms/g, P less than 0.01). These results suggest that changes in pre- or postsynaptic DA receptors may underlie the tolerance and sensitization to the effects of fencamfamine.

Animals↗
PubMed1978

Ergot alkaloids. New ergolines as selective dopaminergic stimulants.

A new two-step sequence for the epimerization of methyl dihydrolysergate (5) at C-8 leading to methyl dihydroisolysergate (7) is presented. The latter compound was used as a starting material for the synthesis of various ergolines, of which (5R,8R,10R)-8-(cyanomethyl)-6-methylergoline (4) is a very strong and long-lasting central dopaminergic agent. Furthermore, it was found that some 8-(arylthiomethyl)-6-methyler-golenes are not able to induce apomorphine-like stereotyped behavior in normal rats but exhibit a remarkable activity in rats unilaterally lesioned by 6-OH-DA in the nigrostriatal region. Compound 4 and (5R,8R)-8-[(2-pyridyl)thiomethyl]-6-methylergolene (9) were further tested for their ability to inhibit ovum implantation and to depress serum prolactin levels in rats. Their potency was evaluated in comparison with (5R,8S,10R)-8-(cyanomethyl)-6-methylergolines (2a and 2b) and 2-bromo-alpha-ergocryptine (1) as standards.

Animals↗
PubMed1977

3,4-Methylenedioxyphenyl-, isopropylidenedioxyphenyl-, and benzyl-substituted chiral 2-aminosuccinimides and 3-aminopyrrolidines. Stereoselective investigations of potential anti-parkinsonian, antipsychotic, and anticonvulsant activities.

The chiral title compounds 2--11 were assessed for their potential anti-Parkinsonian, antipsychotic, and anticonvulsant properties. The most striking differences in the biological activity of enantiomeric pairs were noted for D-(R)-2-amino-N-(3,4-methylenedioxyphenyl)succinimide hydrochloride (2) vs. L-(S)-3 and D-(R)-2-amino-N-(3,4-isopropylidenedioxyphenyl)succinimide (4) vs. L-(S)-5. D-(R)-2-partially attenuated amphetamine-induced stereotyped behavior, whereas D-(R)-4 antagonized oxotremorine-induced tremors. Their respective enantiomorphs were inactive in these tests. No differences in anticonvulsant potency of enantiomeric pairs were observed. The stereoselective actions of D-(R)-2 and 4 were rationalized on the basis of the presence or absence of gem-dimethyl functions in isopropylidenedioxy vs. methylenedioxy groups; the data seem to indicate that these methyl groups influence selective receptor site interaction in the D-(R) series.

Animals↗
PubMed1985

Antagonism of L-5-hydroxytryptophan-induced head twitching in rats by lisuride: a mixed 5-hydroxytryptamine agonist-antagonist?

Lisuride antagonized L-5-hydroxytryptophan (5-HTP)-induced head twitches at doses lower than those sufficient to induce the serotonin (5-HT) syndrome. Among several other 5-HT agonists tested, only LSD and 1-(m-trifluoromethylphenyl)-piperazine (TFMPP) shared this paradoxical profile. Assessment of various dopamine (DA) agonists revealed a lack of correlation between DA-mediated stereotyped behavior (indicative of postsynaptic DA agonism) and blockade of 5-HTP-induced head twitches. Lisuride displaced specific ligand binding from putative S1a, S1b and S2 receptors at nanomolar concentrations, and other drugs that blocked 5-HTP-induced head twitches also displaced binding at S2 sites. It is proposed that lisuride may have agonist properties at S1a receptors mediating the 5-HT syndrome but antagonist properties at S2 receptors mediating 5-HTP-induced head twitching.

5-Hydroxytryptophan↗
PubMed1987

Analysis of demand conditions associated with stereotypy.

Possible escape/avoidance functions of stereotypic behavior were investigated in a classroom setting using functional academic tasks. A 6-year-old boy's stereotypic mouthing was assessed during high vs low response activities, familiar vs novel activities and avoidance vs partial-avoidance conditions. Results showed that stereotypy occurred at higher rates during more difficult activities (i.e. those that were novel or required a greater number of responses), and when stereotypy was allowed to effect a delay in instructional demands. Treatment procedures based on these analyses were implemented by the classroom teacher and shown to be effective.

Avoidance Learning↗
PubMed1988

Intra-cerebral cysteamine infusions attenuate the motor response to dopaminergic agonists.

Previous studies have suggested that somatostatin neurons in the basal ganglia may be involved in motor activity. In the present experiments, the effects of cysteamine, a drug which reduces somatostatin levels, on the basal and dopamine-mediated motor activities were examined in the rat. Neither intra-striatal nor intra-accumbens infusions of cysteamine had any effect on motor activity prior to the administration of dopamine agonists. However, intra-striatal cysteamine infusions reduced the duration of the stereotypic behavior induced by systemic apomorphine. In addition, intra-accumbens infusions of cysteamine produced a slight reduction in the locomotor response induced by amphetamine. The direct intra-cerebral infusion of cysteamine produced a significant depletion in the levels of somatostatin at the site of injections as measured by radioimmunoassay. These results indicate that somatostatin neurons in the basal ganglia may modulate the motor responses following dopaminergic activation, and further support the presence of a dopamine-somatostatin interaction in this region.

Animals↗
PubMed1982

Antiemetic specificity of dopamine antagonists.

Twelve antagonists of apomorphine-induced emesis in dogs were studied in different tests to evaluate their antiemetic specificity. Ten of these antagonists were neuroleptics: benzquinamide, clebopride, bromopride, prochlorperazine, haloperidol, chlorpromazine, thiethylperazine, metoclopramide, droperidol, and pimozide blocked conditioned responding in dogs and apomorphine-induced stereotyped behavior in rats. The use of these compounds as anti-emetics entails a risk of neurological side effects. Metopimazine and domperidone were devoid of neuroleptic activity. Metopimazine, however, showed potent alpha-adrenergic blocking activity, showed histamine H1 antagonism, and induced palpebral ptosis. Therapeutic doses of metopimazine are, therefore, likely to produce sedation and side-effects related to autonomic blockade, Domperidone showed potent antiemetic activity and, up to high doses, no other central or peripheral effects. Therefore, domperidone is the only specific antiemetic known.

Animals↗
PubMed1977

Cerebral dopamine agonist properties of some 2-aminotetralin derivatives after peripheral and intracerebral administration.

A series of variously N-substituted 2-aminotetralins having OH groups at 5 and 6 and at 6 and 7 positions, as well as nonoxygenated systems, has been evaluated for central dopaminergic effects. Stereotypical behavioral effects (sniffing, compulsive gnawing, and hyperactivity) produced by direct intracerebral administration of some of the agents were shown to differ strikingly from responses resulting from peripheral administration. The centrally mediated responses of hyperactivity and sterotypical gnawing-biting head and limb movements were shown to be separable in some test compounds. An improved route to 2-aminotetralin systems has been utilized for some of the compounds, which involves Pummerer rearrangement and cyclization of beta-keto sulfoxides and reductive amination of beta-tetralones with a NaBH4-carboxylic acid complex.

2-Naphthylamine↗
PubMedDate not supplied

The pharmacology of 1-phenyl-2-propylamino-pentane (PPAP), a deprenyl-derived new spectrum psychostimulant.

The peculiar tyramine uptake inhibitory effect of (-)deprenyl prompted structure-activity relationship studies aiming to develop new spectrum central nervous system stimulants which are devoid of MAO inhibitory potency and operate de facto as indirectly acting, nonreleasing sympathomimetics. Of the derivatives synthesized for this purpose, 1-phenyl-2-propylaminopentane (PPAP) was selected as the reference substance and its pharmacological spectrum is presented. PPAP is taken up by the catecholamine axon terminal membrane and the vesicular membrane but it is devoid of catecholamine-releasing property. As a result, PPAP is, by interference, a potent inhibitor of the uptake of indirectly acting sympathomimetic releasers and of the catecholamine transmitters. This was proved, on the one hand, by measuring the uptake of [14C]PPAP into the catecholaminergic axon terminals and the inhibition of the uptake of [3H]noradrenaline and [3H]dopamine by PPAP in the rat brain, and, on the other hand, on the pulmonary artery strip of the rabbit and, in vivo, using the rat nictitating membrane as a detector. PPAP increases motility at 2 mg/kg and, in contrast to amphetamine, inhibits it at very high doses (50 mg/kg) only. A two-sided antagonism in the motility-increasing effect between PPAP and amphetamine and, more pronounced, between PPAP and mazindol was detected. PPAP is substantially less effective in inducing stereotyped behavior than either amphetamine or methamphetamine. PPAP facilitates learning and retention, is highly potent in antagonizing the tetrabenazine-induced depression in behavioral tests and is very effective in the forced swimming test. Whereas amphetamines facilitate performance in a very narrow range of low doses, which turns, at a modest elevation of the dose, into the opposite effect, PPAP improves performance within a reasonably broad dose range. Based on the peculiar pharmacological profile of PPAP, its potential usefulness in depression, in Alzheimer's disease and in attention-deficit-hyperkinetic disorder seems to be plausible.

Animals↗
PubMed1993

Cholinergic mechanisms in startle and prepulse inhibition: effects of the false cholinergic precursor N-aminodeanol.

We examined the effects of cholinergic deficiency on prepulse inhibition (PPI) of the acoustic startle. Rats treated with a choline-free diet that contained the false cholinergic precursor N-aminodeanol showed great deficit in PPI. This deficit does not appear to be secondary to an increase of stereotyped behaviors. Startle threshold was also greatly reduced, as these rats startled to the 70-dB prepulse and the baseline startle amplitude was increased by 60% over the control rats. Arecoline (4 mg/kg) partially reversed the deficit in PPI. This improvement persisted beyond the period of drug treatment. On the other hand, scopolamine (1 mg/kg) reduced PPI in the control rats. These results suggest that cholinergic systems play a major role in both the elicitation and prepulse inhibition of startle.

Acoustic Stimulation↗