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PubMed1994

The role of adrenoreceptors in control of stereotyped oral behavior in restricted-fed fowls.

Effects on environmentally induced oral stereotypies (object pecking and drinker-directed activity) of preferential antagonists and agonists of adrenoreceptor subtypes were examined in individually caged broiler breeder fowls subjected to chronic food restriction. Three drugs in each category were injected intravenously at three doses, and their effects compared with a saline control treatment. With the antagonists, object pecking was suppressed more by prazosin (alpha 1) and propranolol (beta) than by yohimbine (alpha 2), while drinker-directed activity showed delayed stimulation with yohimbine and propranolol. With the agonists, drinker-directed activity was suppressed more by clonidine (alpha 2) than by isoproterenol (beta) and phenylephrine (alpha 1), while object pecking was inhibited by the high doses of clonidine and isoproterenol but showed delayed stimulation with the low dose of clonidine and (nonsignificantly) the high dose of phenylephrine. Initial suppression of both oral stereotypies by the high doses of yohimbine and isoproterenol, and high and medium doses of clonidine, may have been due to sedation, because in those instances it coincided with increased sitting, an activity not normally seen. Increased standing with clonidine and the medium dose of yohimbine may also reflect sedation. When there were no significant increases in sitting or standing to indicate sedation, responses of both stereotypies were essentially the same with all three adrenoreceptor subtypes; i.e., object pecking was inhibited by the antagonist but not the agonist, while drinker-directed activity was inhibited by the agonist but not the antagonist. It is concluded that alpha 1, alpha 2, and beta adrenoreceptors are all implicated in expression of these stereotypes, and that the two activities may be differentially controlled.

Adrenergic alpha-1 Receptor Agonists↗

PubMed1981

A comparison of the effects of neuroleptics on phencyclidine-induced behaviors in the rat.

The dose-response effects of neuroleptic pretreatment on phencyclidine (PCP; 3 or 5 mg/kg)-induced locomotor activity, stereotyped behaviors and ataxia were quantified in groups of male rats using rating scales recently developed in this laboratory. Three butyrophenone neuroleptics consistently produced dose-dependent antagonism of the behavioral effects of PCP administration. Fluphenazine antagonized the behavioral effects produced by 3 mg/kg PCP but not those produced by 5 mg/kg PCP. Each of the other neuroleptics examined (chlorpromazine, thioridazine, mesoridazine, triflupromazine, cis-flupenthixol) had no consistent antagonistic effect or actually enhanced one or more of the behavioral effects of PCP. Some neuroleptics slightly reduced PCP locomotion or stereotypies at high doses, but these effects were probably a non-specific consequence of the synergistic ataxia-producing properties of these drugs. In a second set of experiments, atropine sulfate pretreatment increased PCP-induced locomotor activity and stereotyped behaviors but had no effect on ataxia; pretreatment with physostigmine produced opposite effects. Combined pretreatment with haloperidol and atropine sulfate significantly reduced only haloperidol antagonism of PCP-induced ataxia, thus suggesting that non-dopoaminergic effects of neuroleptics may interfere with their ability to antagonize PCP.

Animals↗

PubMed1988

Neuromuscular patterns of stereotypic hindlimb behaviors in the first two postnatal months. II. Stepping in spinal kittens.

From birth to postnatal day 60, neuromuscular patterns for airstepping and treadmill stepping were assessed in kittens spinalized (T12) at birth (Day-1) or at the end of the second postnatal week (Day-14). Within 72 h after spinalization, all kittens displayed stepping motions, but exteroceptive facilitation (e.g. tail pinch) was required to initiate and sustain both behaviors. In Day-14 spinal kittens, the hindlimbs spontaneously and alternately airstepped, but in Day-1 spinal kittens exteroceptive stimulation was usually necessary to evoke airstepping, and the hindlimbs stepped synchronously. Kittens in both groups developed atypical neuromuscular patterns; flexor bursts were nearly twice as long in duration as extensor bursts. Development of bipedal treadmill stepping was similar for Day-1 and Day-14 spinal kittens, but differed from that for normal kittens. Tested at the same belt speeds, stepping was more easily elicited in spinal kittens, bouts of repetitive stepping were longer, and cycle periods were shorter than in normal kittens until postnatal week 6. Spinal kittens, however, seldom exhibited adequate weight support during hindlimbs stepping, and the neuromuscular patterns associated with bipedal stepping were atypical. For spinal kittens, the relationship between the extensor burst duration and the cycle period was reduced substantially, and flexor activity was initiated earlier in the step cycle and was longer in duration than that for normal kittens. These atypical intralimb synergies may have been the consequence of altered lumbosacral circuits produced by the spinal transection. It is also possible that these spinal circuits, lacking rostral input, were particularly susceptible to abnormal motion-dependent feedback resulting from reduced hindlimb weight support.

Animals↗

PubMed1994

Effect of conditioning with d-amphetamine on the extracellular concentration of dopamine and its metabolites in the striatum of behaving rats.

The effect of classical conditioning with d-amphetamine on the extracellular concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of awake, freely moving rats was studied using microdialysis. This was done in order to test, whether there occurred alterations in DA release as conditioned responses in the striatum. The first series of experiments studied the acute effects of d-amphetamine on the concentration of DA and its metabolites DOPAC and HVA. d-Amphetamine (2 mg/kg, s.c.) increased extracellular DA and decreased DOPAC and HVA. Behaviorally, it led to stereotyped locomotor activation and sniffing. In principle, these observations confirmed earlier findings. In a second series, conditioned responses to d-amphetamine were studied. Rats were implanted with guide cannulas prior conditioning experiments started. For conditioning experiments, the rats were divided into three groups: conditioned group, pseudoconditioned group and a drug-naive control group. After 7 daily training sessions with d-amphetamine (2 mg/kg), on the 8th day, the test day, rats were injected with saline and exposed to the conditional stimuli, while they were observed for their stereotyped, conditioned response. Additionally, microdialysis was performed in order to observe possible changes in the extracellular transmitter or metabolite concentrations. Conditioning with amphetamine led to conditioned stereotypic behavior. In comparison with the pseudoconditioned rats, there was an increase in DA release as conditioned response to amphetamine. In pseudoconditioned rats. DOPAC and HVA were slightly higher than in both other groups. DOPAC and HVA were lower in rats conditioned to d-amphetamine when compared with the pseudoconditioned ones.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed2003

Effects of NRA0045, a novel potent antagonist at dopamine D4, 5-HT2A, and alpha1 adrenaline receptors, and NRA0160, a selective D4 receptor antagonist, on phencyclidine-induced behavior and glutamate release in rats.

RATIONALE: Administration of phencyclidine (PCP) to animals produces abnormal behavior such as hyperlocomotion, stereotyped behavior, and ataxia; this abnormal behavior is only weakly blocked by dopamine D(2) receptor antagonists. This study examined the effects of a novel thiazole derivative, NRA0045 which potently antagonizes not only dopamine D(4) receptors but also 5-HT(2A) and alpha(1) adrenaline receptors, and NRA0160, a selective dopamine D(4) receptor antagonist, on PCP-induced abnormal behavior, and accompanying increases in extracellular levels of glutamate in the medial prefrontal cortex. Furthermore, this study compared the effects of these drugs with those of clozapine and haloperidol. METHODS: To study the effects of NRA-drugs, atypical and typical antipsychotics, we measured locomotor activity with an infra-red sensor, and stereotypy and ataxia on a rating scale. Extracellular glutamate levels were measured by in vivo microdialysis. RESULTS: NRA0045 (1 or 3 mg/kg) or clozapine (1 mg/kg) attenuated hyperlocomotion, stereotypy, and ataxia induced by PCP (7.5 mg/kg) without affecting behavior after saline injection. Although haloperidol (0.1 or 1 mg/kg) attenuated or inhibited PCP-induced behavior, this drug also affected behavior after saline injection. NRA0160 (0.1, 1, or 3 mg/kg) had no effect on behavior induced by PCP or saline. NRA0045 (3 mg/kg), but not NRA0160, inhibited PCP-induced increases in glutamate levels in the medial prefrontal cortex. PCP-induced hyperlocomotion correlated with the PCP-induced increases in glutamate levels in this brain region. CONCLUSIONS: These results suggest that the effects of NRA0045 on PCP-induced abnormal behavior are similar to those of the atypical antipsychotic clozapine. NRA0045 probably attenuates PCP-induced abnormal behavior by inhibiting the PCP-induced increase in glutamate levels in the medial prefrontal cortex; this inhibition may be mediated via the blockade of 5-HT(2A) receptors.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2002

Trichotillomania and skin-picking: a phenomenological comparison.

Although trichotillomania and pathological skin-picking are both characterized by repetitive self-injurious stereotypic behaviors, the former is classified as an impulse control disorder, while the latter is not given a specific diagnostic category in the Diagnostic and Statistical Manual of Mental Disorders (4th edition) [APA, 1994]. There are, however, few empirical data on phenomenological similarities and differences between these disorders. Patients with trichotillomania and pathological skin-picking were compared in terms of several demographic (age, gender), clinical (comorbid axis I and II disorders), and personality variables. Trichotillomania and pathological skin-picking were very similar in demographics, psychiatric comorbidity, and personality dimensions. Dissociative symptoms may be more common in trichotillomania than in pathological skin-picking. These data support the concept of phenomenological overlap between trichotillomania and pathological skin-picking. Future work to assess the implications of overlap for clinical evaluation and intervention in the two conditions may be useful.

Adult↗

PubMed2000

Clinical characteristics and treatment responses in cases diagnosed as reactive attachment disorder.

The aim of our study is to report the relation between pathological care and impairment in social interaction, communication, language development, and stereotypical behaviors. Fifteen cases (9 boys, 6 girls) who have the symptoms listed above and who were misdiagnosed with pervasive developmental disorder (PDD), were referred to our clinic for evaluation and treatment. After the cases were evaluated by a semi-structured interview, symptoms related to pathological care were fortified; maternal depressive symptoms associated with child neglect and overexposure to television viewing. The cases and the mothers/primary caretakers were treated in a standardized psycho-educational program of 3 months. After this period improvements were observed in all of the symptom clusters. Twelve cases (80%) had improvements in eye contact. Eleven cases (73.3%) began to engage in reciprocal play and ten cases (66.6%) showed social imitative behaviors. Six cases (40%) began to form sentences. Stereotypic behaviors diminished in six cases (40%) and disappeared in nine cases (60%). According to our findings, although the symptoms of PDD and reactive attachment disorder (RAD) resemble each other, presence of pathological care and good response to treatment in RAD can be important for the differential diagnosis with PDD.

Child Abuse↗

PubMed1984

Augmentation of sensitivity to ambulation-increasing effect of apomorphine induced by repeated administration in mice.

Effect of apomorphine on ambulatory activity in mice was investigated after single and repeated administration. The activity was measured by a tilting-type round activity cage of 20 cm in diameter. Single administration of apomorphine at doses of 0.016-0.13 mg/kg sc tended to decrease the ambulatory activity, while doses of 0.5-4 mg/kg sc increased it. Repeated administration of apomorphine (0.5 mg/kg sc) at intervals of 1 hr, 1 day and 7 days induced an augmentation of sensitivity to the ambulation-increasing effect of the drug regardless of the administration intervals. The same treatments of apomorphine (1 mg/kg sc) produced neither augmentation nor tolerance to it. However, the mice exhibited stereotyped behaviors such as sniffing and climbing after the repeated administration, although they hardly exhibited the stereotyped behaviors on the 1st administration. The augmentation of sensitivity, once produced, was well maintained 1 month after cessation of the repeated administration. The augmentation of sensitivity to apomorphine was produced in mice which had repeatedly exposed to both experimental situations in which the ambulation was freely allowed and perfectly restricted, respectivity, during presence of the acute drug effect.

Animals↗

PubMed1989

Independent effects of morphine and apomorphine on stereotyped gnawing in the hamster.

Eight experiments were conducted to investigate the effects of apomorphine, a dopaminergic agonist, and of morphine, an opiate, on stereotyped behavior in the hamster. Animals were observed at two minute intervals for one hour and incidents of stereotyped gnawing, licking and sniffing were recorded using a time-sampling method. Both morphine and apomorphine produced dose-related increases in stereotyped gnawing. A low dose of the opiate antagonist, naloxone (0.4 mg/kg), blocked morphine-induced gnawing but neither that dose nor higher doses of naloxone (1, 4 and 10 mg/kg) blocked apomorphine-induced gnawing. A low dose of the dopaminergic antagonist, haloperidol (0.05 mg/kg), blocked apomorphine-induced gnawing but did not block morphine-induced gnawing. Further experiments indicated that morphine administration did not sensitize, or influence in any way, subsequent apomorphine-induced stereotyped behavior.

Animals↗

PubMed1984

Phenytoin potentiates methamphetamine-induced behavior in mice.

We demonstrated that stereotyped behavior and tremor induced by methamphetamine (MA) were potentiated by pretreatment with phenytoin (PNT) in mice. Similar enhancing effects were obtained by pretreatment with carbamazepine. Gas chromatographic study demonstrated that pretreatment with PNT increased MA concentrations in the brain to approximately 2.5 times of control level. The increased MA concentrations were thought to be a major factor for the observed potentiation of MA-induced behavior by PNT. However, all MA-induced behavior were not equally potentiated; tremor was enhanced more than stereotypy. These results suggest that central neuronal mechanisms may also be involved in PNT-potentiated MA-induced behavior in mice.

Animals↗

PubMed1998

(+)-cis-N-ethyleneamino-N-normetazocine derivatives. Novel and selective sigma ligands with antagonist properties.

A series of (+)-cis-N-normetazocine derivatives has been described, and their affinities for sigma1, sigma2, and phencyclidine (PCP) sites and opioid, muscarinic (M2), dopamine (D2), and serotonin (5-HT2) receptors were evaluated. The effect of the N-substitution with a substituted ethylamino spacer was investigated. Compounds 8c-11c displayed high affinities for sigma1 sites and for opioid receptors. Substitution of the second basic nitrogen either with alkyl or cycloalkyl substituents give compounds (1a-6a) with high affinity and selectivity for sigma1 binding sites. Compounds 1a-5a were further characterized in vivo, and their agonist/antagonist activity was evaluated. In mouse, compound 1a and 2a as well as haloperidol suppressed in a dose-related manner the stereotyped behavior induced by (+)-SKF 10,047. Compounds 3a-5a and (+)-pentazocine do not affect the stereotyped behavior induced by ip injection of (+)-SKF 10,047. Therefore, from this series of compounds we identified potent and selective sigma1 ligands which might prove useful to unveil the functional role of sigma1 sites.

Animals↗

PubMed1992

Repeated stimulation of D1 dopamine receptors causes time-dependent alterations in the sensitivity of both D1 and D2 dopamine receptors within the rat striatum.

Recent evidence suggests that repeated stimulation of D1 dopamine receptors within the rat striatum leads to an enhancement of both D1 and D2 dopamine receptor-mediated responses. The present study used both behavioral observations and extracellular single unit recording techniques to investigate this phenomenon following repeated administration of selective D1 dopamine receptor agonists. Groups of rats received twice daily administration of either saline or the partial D1 dopamine receptor agonist SKF 38393 (8 mg/kg, s.c.) for three weeks. Rats were tolerant to the ability of SKF 38393 to enhance grooming behavior when tested immediately following the last of the 42 treatment injections. However, the ability of this last SKF 38393 injection to potentiate oral stereotyped behavior following administration of the D2 DA agonist quinpirole was still evident. Following a one-day withdrawal, grooming responses to SKF 38393 had returned to normal. At this time, administration of quinpirole, without concomitant SKF 38393, failed to significantly promote oral stereotypies, as is typical of normal rats. Following a one-week withdrawal period, SKF 38393-induced grooming behavior was significantly enhanced and quinpirole, administered without SKF 38393, produced pronounced oral stereotyped behavior in 10 of 12 rats tested. Following a one-month withdrawal, these sensitized responses were no longer evident. Single-cell recordings from rat lateral striatal neurons revealed similar time-dependent alterations in the effects of iontophoretically administered SKF 38393 and quinpirole. Current-response curves revealed that, without a withdrawal period, striatal neurons were subsensitive to the inhibitory effects of SKF 38393 but not quinpirole. The decreased inhibitory responses of striatal neurons to SKF 38393 returned to normal levels after a one-day withdrawal. Following a one-week withdrawal, the effects of both agonists were significantly greater than that in saline-treated controls. Normosensitivity was evident following a one-month withdrawal. Repeated administration of the full D1 DA agonist SKF 81297 (0.5 mg/kg, s.c., twice daily) also resulted in sensitized responses of striatal neurons following a one-week withdrawal, demonstrating that the sensitization to SKF 38393 was not due to its partial agonist character. The present findings provide both behavioral and electrophysiological evidence that repeated stimulation of D1 dopamine receptors results in a brief subsensitivity, followed by transient sensitization of the D1 receptors. The enhanced effects of D2 dopamine agonists might be due to an enhanced synergism (enabling) produced by endogenous dopamine stimulating supersensitive D1 receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

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

PubMed1989

Amphetamine stereotypy in cats and neurotransmitter interactions in the caudate nucleus. III. Effects of intracaudate injections of quipazine, cyproheptadine and electrical stimulation of the raphe dorsal nucleus.

The effect of quipazine and cyproheptadine injected into the rostrodorsal part of the caudate nucleus on spontaneous and amphetamine-induced stereotyped behavior was investigated in free moving cats. Quipazine increased focused and even more locomotor (non-focused) stereotyped behavior, augmented the contralateral head movements and decreased the ipsilateral ones. Cyproheptadine decreased focused stereotypy but increased locomotion and the ipsilateral head movements. These results suggest that the serotonin (S-HT) innervation in the region investigated (rostrodorsal caudate nucleus) has an action synergic with that of dopamine released by amphetamine, i. e. if the inhibitory DA receptors prevail over the excitatory ones in this part of the caudate nucleus, the 5-HT receptors are probably also inhibitory. However, electrical 10-Hz stimulation of raphe dorsal nucleus (RD) induced a short-term decrease in all stereotyped movements. This findings suggest that the 5-HT innervation of the caudate nucleus has a much more complex character and that the influences from RD could be different from those of treatments which stimulate the 5-HT receptors (at least in the rostrodorsal part of the caudate nucleus).

Amphetamine↗

PubMed1992

[Behavioral assessment of neuroleptics (2)--stereotypy].

This paper describes the definition of stereotypy and the different methods available for measuring both the form and the invariance of stereotyped behavior. With respect to the use of stereotypy for screening antipsychotic drugs, commonly used techniques for observing dopamine agonist-induced oral stereotypy in rats and the relevant points to analyze in the results are discussed. Apart from the ways of visually analyzing stereotyped behavior, some approaches for quantifying the intensity of stereotypy by using automated systems are also discussed.

Animals↗

PubMed1996

Effects of repeated treatment with methamphetamine plus scopolamine and methamphetamine on behavioral sensitization and conditioning.

This study compared repeated treatment with methamphetamine (4.0 mg/kg, i.p.) plus scopolamine (0.5 mg/kg, i.p.) and methamphetamine alone in behavioral sensitization and drug conditioning with respect to a reciprocal balance between the dopaminergic and cholinergic systems. Repeated methamphetamine plus scopolamine treatment induced a more progressive and enduring enhancement of stereotyped behavior than repeated methamphetamine treatment. Methamphetamine plus scopolamine-induced stereotyped behavior was reproduced by challenge injections of not only methamphetamine plus scopolamine and methamphetamine, but also, to a lesser extent, by scopolamine challenges. The methamphetamine plus scopolamine-sensitized rats were conditioned to a low-frequency tone (300 Hz, 100 dB) as conditioned stimulus associated with the drug state. They responded to pairings of the tone and placebo injections, but not to the tone alone or the placebo alone. The methamphetamine-sensitized rats failed to exhibit conditioning. These results suggest that methamphetamine plus scopolamine-induced pronounced behavioral sensitization may produce an enhanced conditioning. Exteroceptive conditioned stimulus-interoceptive unconditioned stimulus associations may provide an important source for drug conditioning. We concluded that behavioral sensitization may be mediated via a reciprocal balance between the dopaminergic and cholinergic systems, in favor of a dopaminergic dominance. Conditioning to the drug-associated tone may operate via a reciprocal balance between the dopaminergic and cholinergic systems.

Animals↗

PubMed1978

Further analysis of the resistance of the diabetic rat to d-amphetamine.

Rats that were made diabetic by the subcutaneous injection of alloxan monohydrate were found to be resistant to the anorexic action of d-amphetamine. This resistance to amphetamine anorexia did not appear attributable to an increased hunger motivation of the diabetic rats, but rather seemed due to a diminished action of the drug in alloxan-injected animals. This conclusion was supported by further experiments indicating that alloxan-injected rats show diminished locomotor activity and stereotyped behavior following amphetamine administration. Furthermore, the amphetamine resistance appears to be the result of the diabetic state, since amphetamine-induced stereotyped behavior could be reinstated in alloxan-injected rats by the administration of protamine zinc insulin for ten days. The results of these investigations suggest that there exists an altered central nervous system response to d-amphetamine in the diabetic rat. These possibility of an abnormal functioning of central catecholamine-containing neurons in such animals is discussed.

Animals↗

PubMed1991

Estradiol enhances behavioral sensitization to cocaine and amphetamine-stimulated striatal [3H]dopamine release.

Locomotor activity and stereotypy induced by cocaine is increased or 'sensitized' after repeated cocaine administration. This behavioral sensitization may be mediated by a persistent increase in dopamine (DA) transmission in mesolimbic and nigrostriatal pathways. Since the female estrous cycle and ovarian steroid hormones appear to affect both cocaine sensitization and DA transmission, studies were undertaken to determine the effects of ovarian steroids on sensitization of the behavioral responses to repeated cocaine injections and any concomitant effects on striatal DA release. Young female adult rats were ovariectomized and 2 weeks later were implanted with chronic release forms of estradiol (E), progesterone (P), both (EP) or vehicle (V). Locomotor and stereotypic behavior were rated after an initial injection of either saline or cocaine (10 mg/kg, i.p.) and after the 8th daily injection of saline or cocaine. A significant increase in both locomotor and stereotypic behaviors was seen after the first cocaine injection relative to saline-injected animals and this response was not affected by steroid treatment. Repeated injections of cocaine caused sensitization of the initial behavioral response to cocaine (i.e. an increase in stereotypic and locomotor behavior) and the degree of cocaine sensitization was greatest in group E. Steroid treatment did not affect behavior in saline-treated rats. When striatal [3H]DA release was measured in vitro 1 or 7 days after the last injection, amphetamine-stimulated release was greater in vehicle-treated rats 7 days after cocaine injections but not 1 day after injections. In contrast, release was enhanced in group E both 1 and 7 days after cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

PubMed1987

A functional separation of behavioral stereotypy based on naloxone-reversible effects of seryl enkephalinamide: comparison with morphine.

Amphetamine's stereotypic behavioral actions, produced by the stimulant at a moderate dose, were inhibited by the systemic administration of seryl enkephalinamide, D-Ser2-D-Ser5-enkephalinamide, (Wy 42,896). The classical sequelae of stimulatory behavioral events: sniffing, head bobbing, rearing and locomotor activity, were significantly inhibited by the seryl enkephalinamide. Subsequently, pretreatment with the opiate receptor antagonist, naloxone, significantly blocked the inhibitory effects of the seryl enkephalinamide on the stereotypic and locomotor components. Concomitantly, the behavioral stereotypic component, licking, a behavior usually produced by opiates and only high doses of amphetamine, was significantly induced by the seryl enkephalinamide. Pretreatment with naloxone on the stimulatory behavioral effect of licking, produced a significant inhibitory effect. The combination treatment, consisting of both the seryl enkephalinamide and the stimulant amphetamine, caused a naloxone-reversible synergistic effect. These data show that the seryl enkephalinamide, produced concomitant, naloxone-reversible, inhibitory and stimulatory behavioral stereotypic effects. These data are discussed within the context of current neuronal theories which might underly the observed dose-related continuum of behavioral stereotypies produced by morphine and amphetamine.

Amphetamine↗