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Results for “Stereotyped Behavior”

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PubMed1993

Interactions between chronic haloperidol treatment and cocaine in rats: an animal model of intermittent cocaine use in neuroleptic treated populations.

This experiment investigated the possibility that rats maintained on chronic haloperidol treatment would show increased behavioral responsiveness to cocaine, similar to that observed in human stimulant abusers who are chronically treated with neuroleptics. Thus, the effects on locomotion and stereotyped behavior of intermittent injections of cocaine were investigated in female rats receiving chronic haloperidol treatment. Daily injections of haloperidol (0.2 mg/kg, IP) or vehicle were administered for 6, 12 or 18 days prior to the start of testing with cocaine and were then continued throughout cocaine testing. All rats received four doses of cocaine (0.0, 3.0, 7.5, or 15.0 mg/kg, IP) in random order with an intervening vehicle day between successive drug days. The four dose sequence of cocaine was repeated a total of four times. Initial cocaine administration produced dose dependent increases in locomotion and stereotyped behavior. When the sequence of cocaine doses was repeated, differences among treatment groups emerged. Groups treated with haloperidol exhibited heightened locomotion in response to cocaine and with repeated injections, showed a higher rate of behavioral sensitization than control animals. These differences in the behavioral response to cocaine were maintained for at least 2 months following termination of daily haloperidol treatment. In order to examine the mechanisms underlying this heightened responsiveness to cocaine, apomorphine-induced locomotion (dose range, 0-250 micrograms/kg, SC) was determined. Regardless of dose, rats treated with haloperidol showed different temporal patterns of locomotion in response to apomorphine suggesting that the increased response to cocaine was related to changes in dopaminergic receptor sensitivity.

Animals↗

PubMed1979

Rat dopamine hypersensitivity. I. Effect of age.

Two groups of 5 Sprague-Dawley rats were tested with either d-amphetamine or saline following our drug abuse-kindling model for dopaminergic hypersensitivity on pretest and posttest. However, when the animals were 40 weeks older, the saline group also received d-amphetamine. Thus, this group served as saline control for the initial two tests and-amphetamine control for age on the third session. The control group showed significantly more stereotyped behavior on Phase 3 as compared with the experimental group in the first session. These results suggest an increased responsivity of dopaminergic receptors with age as measured by stereotyped behavior in rats.

Age Factors↗

PubMed2001

Behavioral effects of the aqueous extract of Guiera senegalensis in mice and rats.

Behavioral effects of the aqueous extract of Guiera senegalensis on the central nervous system of mice and rats were investigated. Spontaneous motor activity, pentobarbital sleeping time, amphetamine-stereotyped behavior, exploratory activity and performance on treadmills (rota-rod) were evaluated. The results revealed that the aqueous extract of G. senegalensis reduced spontaneous motor activity in mice, prolonged the duration of pentobarbital sleeping time in rats and attenuated amphetamine-induced stereotype behavior in rats. The extract also decreased exploratory activity in mice and had no observable effects on motor coordination (rota-rod) at the doses tested. The results suggested that the crude aqueous extract of G. senegalensis possesses some biologically active principles that are sedative in nature.

Amphetamine↗

PubMed1996

Behavioral responses induced by repeated treatment with methamphetamine alone and in combination with scopolamine in rats.

Repeated amphetamine (A) or methamphetamine (M) treatment induces behavioral sensitization and drug conditioning. The present study compared behavioral sensitization and drug conditioning between treatments with M combined with scopolamine (S) and M alone with respect to a reciprocal balance between the dopaminergic and inhibitory cholinergic systems in rats. Repeated treatment with M (4.0 mg/kg i.p.) combined with S (0.5 mg/kg i.p.) (MS) produced progressive enhancement of stereotyped behavior, compared with repeated M treatment alone. Repeated MS treatment induced focussed stereotyped behavior that was elicited by every challenge injection of not only MS and M, but also partially by S. MS- but not M-sensitized rats exhibited conditioned responses to a tone (300 Hz, 100 dB) associated with drug state, suggesting that MS-induced pronounced behavioral sensitization may lead to an enhanced conditioned response to the conditioned stimulus (CS) of a tone. It is suggested that MS-induced behavioral sensitization may be mediated via a reciprocal balance between the dopaminergic and cholinergic systems in favor of a dopaminergic dominance, and that such a balance may be involved in the conditioning to the drug-associated tone CS.

Animals↗

PubMed1989

Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdialysis.

This study examined the acute effects of the novel antidepressant drug, bupropion, on extracellular concentrations of dopamine (DA), its metabolites, and the serotonin metabolite 5-HIAA in the striatum and nucleus accumbens using on-line microdialysis in freely moving rats. Bupropion HCl (10, 25, and 100 mg/kg intraperitoneally) increased extracellular striatal DA in a dose- and time-dependent manner; 1 mg/kg did not affect extracellular DA. The maximal response occurred within the first 20 minutes (+76%, +164%, and +443% for each dose, respectively) followed by a gradual decrease to a stable but elevated level for the next 2 hours. This neurochemical response was strongly associated with bupropion-induced stereotyped behavior during the first hour but not during the subsequent 2 hours. Bupropion decreased DOPAC concentrations, increased 5-HIAA, and had variable effects on homovanillic acid (HVA) (decreases with 10 mg/kg and increases with 25 and 100 mg/kg). The increase in extracellular DA after bupropion (25 mg/kg) was blocked by tetrodotoxin and was therefore action-potential-dependent. Bupropion produced similar neurochemical responses in the striatum and the nucleus accumbens. These results suggest that increases in DA transmission contribute to the behavioral effects of bupropion and are consistent with a role for DA in the antidepressant effects of this drug. The partial dissociation between DA release and stereotyped behavior suggests that the relationship between neurotransmitter release and behavior may be complex.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Exploring the experience of autism through firsthand accounts.

Two firsthand accounts from verbal, high-functioning individuals with autism are presented. Participants include a 27-year-old man and a 13-year-old boy and his parents. Data collection included participant observation, formal and informal interviewing, correspondence, and collection of personal documents such as poems, art work, and essays. It was our aim to explore the participants' perceptions, mental processes, and experiences of living with autism. Five salient themes are identified and discussed: sensory processing, memory, stereotypical behaviors, social interaction, and empathy. Multichanneled sensory processing appeared in both participants, as well as a remarkably detailed memory of past events. Both participants were able to bring their stereotypical behaviors under voluntary control as a result of their awareness of nonautistic individuals' reactions to these behaviors.

Adaptation, Psychological↗

PubMed2001

Changes in the performance of schedule-induced polydipsia (SIP) in rats after arecoline and amphetamine treatments.

This study investigated the performance of schedule-induced polydipsia (SIP) rats in novel or intermittent-reward SIP sessions after arecoline (AREC) and amphetamine sulfate (AMPH) treatments. Either automatic monitors or observers extensively examined the functional changes of parameters in behavioral performance followed by increasing drug dosage. The parameters included locomotion and stereotyped behaviors in the novel sessions; schedule-induced licks, water intake, schedule-dependent nose-pokes, pellets earned and stereotyped behaviors of the facultative stage in the SIP sessions. It was found that when the rats received AMPH (0.5 - 2.0 mg/kg) but not AREC (0.1 - 1.6 mg/kg) in the novel sessions, locomotion increased in a dose-dependent manner. However, when AREC (0.8 mg/kg) and AMPH (1.0 mg/kg) were both given, the effect of AMPH on locomotion was significantly attenuated. In the SIP sessions, a single injection of AMPH increased the number of schedule-dependent nose-pokes at a dose of 1.0 mg/kg, whereas it decreased the number of schedule-induced licks and the amount of water intake at a dose of 2.0 mg/kg. On the other hand a single injection of AREC caused no operant behavior changes at doses below 0.8 mg/kg. However, when the dose was increased to over 0.8 mg/kg (1.6 mg/kg), the number of schedule-induced licks and water intake increased, but the number of schedule-induced nose-pokes decreased. The effects of large doses of AREC on SIP were attenuated after co-administration of scopolamine (0.1 mg/kg), a muscarinic receptor antagonist. Furthermore, the effects of AMPH on SIP performance were not changed by co-administration of AREC at a dose of 0.8 mg/kg. These results are discussed based on the hypothesis that combined utilization of the main component in chewing betel quid, AREC, and AMPH may yield changes of AMPH-induced psychomotor responses in a special environmental context.

Animals↗

PubMed1983

Enhanced stereotyped response to amphetamine after pretreatment with small doses of molindone.

Pretreatment of rats with small doses of the antipsychotic drug, molindone, enhanced the stereotyped behavioral response to amphetamine. In order to determine whether molindone enhanced amphetamine-induced stereotypy by the same mechanism as chronic administration of amphetamine or drugs that inhibit central noradrenergic transmission, the effect of these drugs on the stereotyped behavior produced by beta-phenethylamine (PEA) was compared. Following the administration of phenoxybenzamine, reserpine and diethyldithiocarbamate, the stereotyped response produced by beta-phenethylamine was intensified. In contrast, neither molindone nor chronic pretreatment with amphetamine altered beta-phenethylamine-induced stereotypy. As shown previously with chronic amphetamine pretreatment, molindone also failed to enhance the stereotyped response produced by apomorphine. However, in contrast to the effects of chronic administration of amphetamine, molindone both increased the striatal concentration of dihydroxyphenylacetic acid (DOPAC) and blocked the ability of small doses of apomorphine to decrease this dopamine (DA) metabolite. The doses of molindone that blocked the apomorphine-induced reduction in the concentration of DOPAC in the striatum correlated with the doses that enhanced amphetamine-induced stereotypy. Since the decrease in DOPAC in the striatum produced by apomorphine is thought to be mediated through the stimulation of striatal DA autoreceptors, these results suggest that molindone enhances amphetamine-induced stereotypy by selectively inhibiting DA autoreceptors.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Do forebrain structures compete for behavioral expression? Evidence from amphetamine-induced behavior, microdialysis, and caudate-accumbens lesions in medial frontal cortex damaged rats.

The neurochemical basis of behavioral changes following medial frontal cortex damage were investigated. Experiment 1 examined locomotion in response to D-amphetamine (1.5 and 5 mg/kg) in rats that had received bilateral aspirative lesions of the medial frontal cortex alone or in combination with 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens or caudate-putamen. Relative to controls, medial frontal cortex rats were initially hypoactive (day 1 postoperative) but rapidly became hyperactive (days 5-15 postoperative). Locomotor-time profiles and stereotypy ratings showed that amphetamine produced a selective enhancement of locomotion at the expense of stereotyped behavior. Nucleus accumbens lesions blocked the locomotion but enhanced stereotyped behavior in the medial frontal cortex damaged rats, suggesting that amphetamine-enhanced locomotion is dependent upon the integrity of the nucleus accumbens. In Experiment 2, intracerebral microdialysis was used to examine whether alterations in dopamine (DA) or monoamine metabolites in the nucleus accumbens or caudate-putamen accompanied the lesion-induced changes in locomotion. There were no differences in extracellular DA or monoamine levels between control rats and medial frontal cortex rats when tested on day 1 or day 15 postsurgery, either when they were at rest, while they walked on a motor-driven belt, or after amphetamine treatment. Therefore, it seems unlikely that changes in amphetamine-induced locomotion following medial frontal cortex lesions are related to underlying modifications in dopaminergic activity in the nucleus accumbens. It is suggested that neural structures compete for behavioral expression and that postlesion behavioral alterations reveal the competitive advantage of remaining intact neural systems.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1979

Rat dopaminergic hypersensitivity. II. Effects of sex.

Two groups of 5 male and 5 female Sprague-Dawley rats each were tested for dopaminergic hypersensitivity on d-amphetamine or apomorphine following a drug abuse-kindling model. In constrast to the males, the female animals did not develop hypersensitivity on either drug, had a higher baseline stereotyped behavior on low doses of d-amphetamine, and lower baseline for apomorphine. Furthermore, on apomorphine the females showed tolerance instead of hypersensitivity with a significant decrease of stereotyped behavior a posttest as compared with pretest. Female rats do not develop a readily demonstrable dopaminergic hypersensitivity with this procedure and show an absence of reverse tolerance to apomorphine.

Animals↗

PubMed1978

Postsynaptic supersensitivity and kindling: further evidence of similarities.

Fourteen Sprague-Dawley rats of 150 to 200 g of initial weight were given either d-amphetamine or cocaine intermittently following both a drug-abuse model previously described by the author and an intermittent model for pharmacological "kindling." The psychotogenic effects of the drugs were measured as stereotyped behavior utilizing standardized scales. A retest with the same drug and same protocol as the pretest stage was executed after an off-drug period of 12 weeks, demonstrating dopamine receptors hypersensitivity as measured by stereotyped behavior for both d-amphetamine and cocaine. The importance of demonstrating dopamine receptor hypersensitivity with an intermittent (kindling) drug-abuse-type model is discussed.

Animals↗

PubMed1997

Behavioral changes in rats with early ventral hippocampal damage vary with age at damage.

Our previous work demonstrated that neonatal (on postnatal day 7, PD7) excitotoxic damage of the ventral hippocampus (VH) results in delayed emergence of behaviors related to dopaminergic (DA) transmission. In this study, the developmental effects of VH lesions induced at two other ages were investigated in the rat. Ibotenic acid or artificial cerebrospinal fluid was infused into the VH of 3- (PD3) or 14- (PD14)-day-old rat pups. Amphetamine-induced (1.5 mg/kg, i.p.) locomotor activity was assessed in the sham and lesioned rats prior to (PD35) and after puberty (PD56 and PD86). Apomorphine-induced (0.75 mg/kg s.c.) stereotypic behaviors were measured on PD56. Similar VH lesions resulted in different profiles of behavioral abnormalities depending upon the age at which they were induced. The PD3 lesioned rats displayed hyperlocomotion to amphetamine only after puberty, while the PD14 lesioned rats manifest hyperlocomotion as early as 3 weeks after surgery (at PD35). Moreover, the PD3 lesioned rats tended to show more stereotypic behaviors in response to apomorphine than the sham-operated controls, while the PD14 rats had a profoundly diminished stereotypic response. The behavioral changes in the PD3 lesioned rats are reminiscent of those previously described in animals lesioned at PD7. In contrast, the deficits in the PD14 lesioned animals resemble those seen before in rats lesioned in adulthood. These results indicate that the pattern of impairments associated with the excitotoxic VH lesion varies with age at lesion, i.e. a similar pattern seems to be associated with lesions up to PD7, but not by PD14. To the extent that the neonatal VH lesion in the rat models certain phenomenological aspects of schizophrenia, including the temporal pattern of symptom onset, these results provide evidence that the model requires an early defect in limbic cortical development.

Aging↗

PubMed2002

In vitro and in vivo pharmacological profile of 4-(4-fluorobenzylidene)-1-[2-[5-(4-fluorophenyl)-1H-pyrazol-4-yl] ethyl] piperidine (NRA0161).

Atypical antipsychotic properties of 4-(4-fluorobenzylidene)-1-[2-[5-(4-fluorophenyl)-1H-pyrazol-4-yl]ethyl] piperidine (NRA0161) were investigated by in vitro receptor affinities, in vivo receptor occupancies and findings were compared with those of risperidone and haloperidol in rodent behavioral studies. In in vitro receptor binding studies, NRA0161 has a high affinity for human cloned dopamine D(4) and 5-HT(2A) receptor with Ki values of 1.00 and 2.52 nM, respectively. NRA0161 had a relatively high affinity for the alpha(1) adrenoceptor (Ki; 10.44 nM) and a low affinity for the dopamine D(2) receptor (Ki; 95.80 nM). In in vivo receptor binding studies, NRA0161 highly occupied the 5-HT(2A) receptor in rat frontal cortex. In contrast, NRA0161 did not occupy the striatal D(2) receptor. In behavioral studies, NRA0161, risperidone and haloperidol antagonized the locomotor hyperactivity in mice, as induced by methamphetamine (MAP). At a higher dosage, NRA0161, risperidone and haloperidol dose-dependently antagonized the MAP-induced stereotyped behavior in mice and NRA0161 dose-dependently and significantly induced catalepsy in rats. The ED(50) value in inhibiting the MAP-induced locomotor hyperactivity was 30 times lower than that inhibiting the MAP-induced stereotyped behavior and 50 times lower than that which induced catalepsy. These findings suggest that NRA0161 may have atypical antipsychotic activities yet without producing extrapyramidal side effects.

Animals↗

PubMed1978

Spontaneous and amphetamine-induced behavior after bilateral injection of ethanolamine-O-sulfate into the substantia nigra.

Injections of ethanolamine-O-sulfate (EOS) (200 microgram/kg) through chronic indwelling cannulae into the zona reticulata of the substantia nigra in rats produced immediate contraversive turning (away from the injection side). Bilateral injections produced spontaneous stereotyped behaviors including sniffing and biting. Twenty-four hours after the first injection of EOS the rats showed a significantly decreased locomotor response to 1.5 mg/kg D-amphetamine. The spontaneous behaviors elicited following the initial injection of EOS increased both in nature and duration with the second and third injections of EOS, and persevered for 24 h. At this time 1.5 mg/kg D-amphetamine intensified this spontaneous stereotyped behavior. GABA levels were significantly higher in substantia nigra, hypothalamus, corpus striatum and cerebral cortex 24 h following single or repeated (3 x) injections of 200 microgram/kg of EOS into the zona reticulata of the SN. Dopamine levels in the corpus striatum were unchanged 24 h following the EOS treatment except by the injection procedure itself. Control injections into the thalamus produced no turning or stereotypy, nor an enhanced response to 1.5 mg/kg D-amphetamine. GABA levels were, however, significantly higher in the substantia nigra and thalamus 24 h following repeated injections (3 x) of EOS into the thalamus. Results are consistent with the hypothesis that GABA containing neurons comprise part of the efferent output of the corpus striatum and do not act exclusively through a dopaminergic substrate.

Animals↗

PubMed1997

Broader autism phenotype: evidence from a family history study of multiple-incidence autism families.

OBJECTIVE: Studies of families ascertained through a single autistic proband suggest that the genetic liability for autism may be expressed in nonautistic relatives in a phenotype that is milder but qualitatively similar to the defining features of autism. The objective of this study was to examine behaviors that may define this broader phenotype in relatives ascertained through two autistic siblings. METHOD: The authors used a semistructured family history interview to compare the rates of social and communication deficits and stereotyped behaviors in relatives ascertained through two autistic siblings (families with multiple-incidence autism; 25 families) with the rates in relatives of Down syndrome probands (30 families). RESULTS: Higher rates of social and communication deficits and stereotyped behaviors were found in the relatives in the families with multiple-incidence autism. CONCLUSIONS: These data suggest that further studies should be undertaken to delineate the boundaries of the broader autism phenotype and that this broader phenotype should be included in some future genetic analyses of this disorder.

Adolescent↗

PubMed1986

Radio-frequency analysis of the effect of haloperidol and cyclo (leucyl-glycyl) on apomorphine-induced stereotypy.

Our previous studies indicated that the peptide cyclo(leucyl-glycyl) (cLG) prevents the development of supersensitivity to dopamine in several animal models at both biochemical and behavioral levels. We therefore tested cLG in a paradigm more commonly used to model tardive dyskinesia, namely chronic haloperidol administration to rats. We found that cLG administered subcutaneously at a dose of 8 mg/kg, blocked about 50% of the supersensitizing effects of of haloperidol on apomorphine-induced stereotypic behaviors. Further, we used a novel method, radio-frequency analysis, that quantifies sniffing and other stereotypic movements. Unlike methods that rely on visual observation of stereotypy and utilize an ordinal scale, these measurements are rated by an automatic motility monitor and utilize a ratio scale. Unlike other automated motility monitors, this device can distinguish between various forms of stereotypic behaviors. Since parametric statistics can be used, there is a significant improvement in the efficiency of the task of rating and comparing stereotypy scores.

Animals↗

PubMed1984

Determination of functionally-relevant serum levels of MJ 13859-1 in the dog: relationship to blockade of amphetamine stereotypy.

The ability of drugs to block dopamine-agonist induced stereotypy in animals has proven to be a reliable in vivo predictor of antipsychotic efficacy in man. Assessment of a drug's potency at displacing [3H]spiperone from rat striatal membranes is an in vitro test which also has predictive validity for antipsychotic actions. Methods are described for assessing stereotyped behavior in the dog, and for measuring the ability of serum samples taken from treated animals at behaviorally interesting time points, to displace [3H]spiperone from washed synaptic membranes of rat striata. In these studies, oral administration of the potential antipsychotic agent MJ 13859-1 blocked amphetamine-induced stereotyped behavior in the dog for 6 hours. This behavioral effect was accompanied by sustained serum levels of [3H]spiperone displacing moieties derived from MJ 13859-1.

Amphetamine↗

PubMed2005

Behavioral neurotoxicity in adolescent and adult mice exposed to fenproporex during pregnancy.

We investigated the effects of gestational exposure to fenproporex, one of the most used anorectic drugs in Brazil, on the behavior of adolescent and adult pups (30 and 60 days of age, respectively). Pregnant Swiss mice were treated daily, by gavage, with 15 mg/kg of fenproporex chloride or water during the whole gestational period. Male pups were submitted to open-field, forced swimming test, tail suspension test and fenproporex-induced stereotyped behavior. The results demonstrated that gestational exposure to fenproporex induces antidepressant-like effect and decreases fenproporex-induced stereotyped behavior in both adolescent and adult pups. Moreover, fenproporex-exposed adolescent pups tended (P= 0.06) to be more active than control pups. Our data show, for the first time, that gestational exposure to fenproporex leads to long-lasting behavioral toxicity in male mice characteristic of altered dopaminergic transmission.

Amphetamines↗