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PubMed1992

Prediction of cerebral ischemia by ophthalmoscopy after carotid occlusion in gerbils.

BACKGROUND AND PURPOSE: The Mongolian gerbil provides a unique model of unilateral focal cerebral ischemia because of the lack of posterior communicating arteries in all gerbils as well as an absence of an anterior communicating artery in approximately 20% of the gerbil population. It is unclear how to identify unequivocably the subpopulation of animals that would suffer a severe focal cerebral ischemia after unilateral carotid occlusion. METHODS: Ninety-three male gerbils were exposed to unilateral occlusion of the right common carotid artery. The severity of neuronal loss was evaluated histologically in gerbils selected as having significant focal ischemia based on either behavioral criteria (i.e., the demonstration of stereotypical behavior within 1 hour after occlusion) or ophthalmoscopic criteria (i.e., interruption of the retinal arterial perfusion within 10 minutes of carotid ligation as assessed with an ophthalmoscope). After 3 hours of unilateral carotid occlusion, cerebral blood flow was reinstated for 24 hours before fixation for histological analysis. The viability of the CA1 region of the hippocampus, lateral cortex, and medial cortex was scored on a scale of 0-4 based on the percentage of apparent neuronal loss (e.g., 0, no damage; 4, > 75% damage (the Viability Index). RESULTS: Twenty-eight percent of the gerbils met the behavioral selection criteria, and 17% met the ophthalmoscopic criteria. In the specimens selected by behavioral criteria (n = 7), 30% demonstrated no evidence of postischemic neuronal loss; the mean +/- SEM Viability Index scores for CA1, lateral cortex, and medial cortex were 1.6 +/- 0.6, 1.0 +/- 0.3, and 0.3 +/- 0.2, respectively. Of the animals selected by ophthalmoscopic criteria (n = 12), 100% had severe ischemic tissue damage to the ipsilateral hemisphere; the Viability Index scores for CA1, lateral cortex, and medial cortex were 3.5 +/- 0.1, 3.1 +/- 0.2, and 1.2 +/- 0.2, respectively; all scores were significantly larger than those observed in the behaviorally selected group. CONCLUSIONS: Selection of animals by ophthalmoscopic criteria provides a reliable, consistent method to predict animals with severe focal cerebral ischemia.

Animals↗

PubMed1975

Effects of disulfiram on the amphetamine-induced behavioral syndrome in the cat as a model of psychosis.

We have previously reported that, from a phenomenological standpoint, the behavioral manifestations of cats chronically intoxicated with amphetamine parallel the evolution of the paranoid psychosis induced by the drug in humans. However, certain manifestations in the cat, such as frozen postures, disjunctive behaviors and postures, cataleptic-like phenomena, obstinate progression, loss of righting reflex and pupillary changes, did not appear to be consistent with the phenomenology of the paranoid psychosis. Since treatment of schizophrenic patients with disulfiram, an inhibitor of norepinephrine synthesis that acts at the level of the enzyme dopamine beta-hydroxylase, thereby leading to increased dopamine concentrations, had been found to profoundly exaggerate psychotic symptomatology, amphetamine behavioral syndrome in the cat as it is modified by pretreatment with disulfiram. Following such pretreatment, a faster development of certain end-stage components of the amphetamine syndrome was obtained. Thus, on the first day, development of a Reactive attitude and of more prominent behavioral disjunction occurred with the combined drug administration as compared with amphetamine alone. In contrast with the facilitation of these behaviors was the absence of dyskinesias and hyperreflexia on that day. Stereotyped behavior, loss of motor initiative and hyperkinetic activity were markedly enhanced and appeared with a shorter latency period on subsequent days of the intoxication cycle. Loss of righting reflex was an early manifestation in these animals. During the later days, the particularly high level of compulsive activity was evident from the occurrence of an obstinate progression syndrome and the performance of stereotyped movements of the head in the presence of a crucifixion posture. In general, modification of the amphetamine effects on behavior was in a direction consistent with comparable features in experimental catatonia and the catatonic form of schizophrenia. The need to integrate such phenomena in any amphetamine model of psychosis is stressed and analogies are drawn with similar features reported in animals treated with bulbocapnine or other psychotogenic compounds and with symptoms of human amphetamine psychosis and schizophrenia.

Animals↗

PubMed2006

Characterization of the rapid-onset type of behavioral sensitization to amphetamine in mice: role of drug-environment conditioning.

A rapid-onset type of behavioral sensitization (ROBS) has been demonstrated in rats treated with a single 'priming' injection of amphetamine (AMP). In that species, however, this phenomenon was restricted to AMP-induced stereotyped behavior (SB), not occurring for the locomotor-stimulant effect (LSE) of AMP and not reflecting environment-specific sensitization. In the present study, the ROBS was characterized in the mouse. Mice received a single 'priming' intraperitoneal injection of 5.0 mg/kg AMP which was paired or not with environment. At different intervals (3, 4 or 5 h) subgroups were tested for AMP (1.5 or 5.0 mg/kg)-induced SB or AMP (1.5 mg/kg)-induced open-field LSE. Results showed that: (1) in the absence of drug-environment association, a priming injection of AMP increased the SB induced by a 1.5 mg/kg AMP challenge injection given 3 h (but not 4 or 5 h) later; (2) when the dose of AMP challenge injection was increased to 5.0 mg/kg, an enhancement of SB was verified at all the intervals tested (3, 4, and 5 h); (3) when animals were tested in an open field, the priming injection of AMP produced an increase in the LSE of a 1.5 mg/kg AMP challenge injection, given 4 h later; (4) drug-environment association increased both SB and locomotion after a saline challenge injection and potentiated the rapid-onset sensitization of both behaviors in AMP-challenged mice. Collectively, these results demonstrate that the ROBS phenomenon also occurs in mice, is extended to AMP-induced LSE, and is markedly potentiated by (but does not depend on) environmental conditioning.

Amphetamine↗

PubMed1975

The behavioral pharmacology of butaclamol hydrochloride (AY-23,028), a new potent neuroleptic drug.

Butaclamol hydrochloride (AY-23,028) is a member of a new chemical class for which antipsychotic activity in humans has recently been demonstrated. The compound antagonized amphetamine-induced stereotyped behavior in rats, amphetamine toxicity in aggregated mice and apomorphine-induced emesis in dogs. It depressed both discriminated avoidance and continuous lever-pressing behavior in rats and inhibited ambulation and rearing in the open field. At higher doses, AY-23,028 induced catalepsy. Adrenergic blocking activity, measured by the antagonism of epinephrine-induced mortality, was weak. These pharmacological actions are characteristic of neuroleptic drugs. In the dose range where the aforementioned effects were observed AY-23,028 did not antagonize either the tetrabenazine-induced ptosis or the tremorine syndrome and did not cause either hypothermia or ataxia. The potency and onset of action of AY-23,028 were comparable to those of fluphenazine but AY-23,028 was of longer duration. The results are discussed in relation to current concepts of neuroleptic mechanisms.

Amphetamine↗

PubMed1976

Acute tolerance to amphetamine in rats.

Two groups of rats were given amphetamine intravenously at 5-min intervals (5 or 10 mg/kg/h) for 8 h. Two control groups received saline infusions. On the second day a test dose of 10 mg/kg amphetamine was given to all groups. Body temperature, food intake, and motor behavior were registered every 30 or 60 min. The results showed the development of acute tolerance to the hyperthermic effect within 3-5 h. Tolerance was still visible on the 2nd day. There was also tolerance to the anorectic effect, which was evident on the 2nd day. One element of stereotyped behavior (swaying) also decreased during the amphetamine infusions.

Animals↗

PubMedDate not supplied

Embryotoxic and long-term effects of cadmium exposure during embryogenesis in rats.

The present study was performed to evaluate the long-term behavioral effect in offspring of a subteratogenic Cd dose administered by the oral route to Wistar rat during organogenesis. First, the teratogenic Cd dose was determined by treating pregnant rats with 20 mg/kg Cd from Day 6 to Day 14 of pregnancy and by visceral and skeletal analysis of their fetuses. In a second experiment, pregnant rats treated with this Cd dose were allowed to give birth and nurture their offspring. The physical and behavioral parameters of the offspring were analyzed in infancy and during adulthood. Results showed that Cd treatment during organogenesis (1) was not able to induce maternal toxicity; (2) induced external malformations; (3) increased significantly fetus anomalies and malformations, with reduced metacarpus ossification, cleft palate and right or left renal cavitation being observed in these animals; (4) did not modify pup body weight or weight gain during the lactation period; (5) improved testis descent and delayed the vaginal opening of pups; (6) did not modify ear unfolding, incisor eruption, eye opening, negative geotaxis or palmar grasp; (7) did not modify the open-field parameters and the stereotyped behavior of male or female pups; and (8) modified male sexual behavior and (9) reduced female sexual behavior. We conclude that prenatal exposure to a teratogenic Cd dose induced in the survivor animals several deleterious effects in their development as well as in adult behaviors, mainly in the sexual sphere.

Administration, Oral↗

PubMed1993

Gangliosides facilitate the recovery of behavioral response mediated by dopaminergic sites following their irreversible blockade.

The effect of acute and chronic exogenous ganglioside (G) administration on the functional recovery of dopaminergic receptors following their blockade by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was investigated by means of apomorphine (APO)-induced stereotyped behavior. Animals previously treated with EEDQ exhibited a lack of behavioral response to APO 6 or 24 h later. A progressive behavioral recovery was already evident at day 3 and reached control values at day 7. G pretreatment accelerated the behavioral recovery after EEDQ administration, because a higher behavioral response to APO in these animals as compared with rats treated with EEDQ alone at the same time was observed. These findings indicate that G accelerates the functional recovery of dopaminergic sites following their irreversible blockade.

Animals↗

PubMed2005

Enhanced behavioral response to repeated-dose cocaine in adolescent rats.

RATIONALE: Most lifelong drug addiction in humans originates during adolescence. Important structural and functional changes in the brain occur during adolescence, but there has been little direct study of how this impacts on drug abuse vulnerability. An emerging literature suggests that adolescents exhibit different behavioral responses to single doses of several addictive drugs, including ethanol, amphetamine, and cocaine. However, few studies have explored behavioral responses to the repeated dosing that is characteristic of human abuse of these substances. OBJECTIVES: We have investigated age-related behavioral responses to acute "binge" cocaine treatment between adults and adolescents. RESULTS: Adolescent rats displayed an exaggerated behavioral response to cocaine administered in two different binge patterns. Total locomotion after cocaine administration was the same in adolescents and adults. However, adolescent rats engaged in more intense stereotypic behaviors, including paw treading, head weaving, and focused sniffing than adult rats. These differences were observable following a modest dose of cocaine and became more robust following subsequent doses within a binge. Cocaine [corrected] brain levels were not significantly different between age groups during any of the exposure sessions. CONCLUSIONS: These findings suggest that equivalent tissue concentrations of cocaine produce a greater behavioral response in young rats, and that adolescent animals display an apparent form of intrabinge sensitization.

Age Factors↗

PubMed1995

[Reverse-tolerance phenomenon in methamphetamine-induced behavioral stereotypy and impairment of cliff avoidance reaction after subchronic methamphetamine administration in rats].

Clinical evidence of methamphetamine (MAP)-induced reverse-tolerance phenomenon is available in studies of methamphetamine psychosis. To examine the clinical relevance of the reverse-tolerance phenomenon as a model of this psychosis, two experiments were conducted using rats. In the first experiment, we examined the relationship of MAP (4 mg/kg/day)-induced reverse tolerance in behavioral stereotypy to impairment of the cliff avoidance reaction (CAR). The stereotypy scores by the method of Creese and Iversen reached a maximum at day 14, and were unchanged thereafter. Impairment of CAR appeared in 3 of 6 rats at day 21 or 28 without motor ataxia, as rated by the scoring system of Hiramatsu et al. This suggested that cognitive dysfunction reflected by CAR impairment may develop after MAP-induced reverse-tolerance phenomenon, as evaluated by the behavioral stereotyping rating scale. In the second experiment, the effect of PCP (1 mg/kg) on CAR was examined in rats pretreated with MAP (4 mg/kg/day) for 30 days. No behavioral stereotypy or CAR impairment was found in these rats for 1 hour after PCP challenge. This showed that MAP-induced reverse-tolerance did not alter sensitivity to PCP in producing behavioral stereotypy or CAR impairment.

Animals↗

PubMed1989

An evaluation of gentle teaching and visual screening in the reduction of stereotypy.

Gentle teaching and visual screening techniques have been used to control severe behavior problems in persons with mental retardation. An alternating treatments design was used to compare gentle teaching, visual screening, and a task-training condition in the reduction of the high-level stereotypy of 3 persons with mental retardation. Following a baseline phase, a task-training condition using standard behavioral techniques was implemented to establish the effects of training the subjects on the tasks. Results showed a modest decrease in stereotypy. This phase was followed by an alternating treatments phase in which visual screening, gentle teaching, and baseline conditions were compared. Both procedures were superior to the control condition in reducing stereotypic behavior, with visual screening being more effective than gentle teaching. When compared with data from the prior phase, gentle teaching was found to be more effective than task training for 2 subjects but less effective for the 3rd, whose stereotypy increased during gentle teaching. Two succeeding phases in which visual screening was implemented across two and then all three daily conditions reduced stereotypy further to near-zero levels. An additional phase with 1 subject demonstrated that the treatment effects of visual screening were easily replicated across therapists. Mixed and idiosyncratic changes in collateral behaviors occurred. For example, "bonding," the goal of gentle teaching, occurred at the same low levels under both treatments, contrary to the predictions of gentle teaching's proponents. The results indicate that gentle teaching may not be the universal treatment of choice for stereotypy its proponents suggest, and that it requires further empirical evaluation.

Adult↗

PubMed1990

Behavioral effects of Org 2766, a synthetic analog of the adrenocorticotrophic hormone (4-9), in 14 outpatient autistic children.

Fourteen children (12 infantile autism full syndrome present, 2 atypical pervasive developmental disorder) between 5 and 13 years of age participated in a double-blind placebo-controlled cross-over trial. Each child received 20 mg Org 2766 (synthetic analog of ACTH 4-9)/day during 4 weeks, or placebo in a randomly assigned sequence. Drug effects were monitored by ethological playroom observation and by Aberrant Behavior Checklist ratings by parents and teachers. Data of the playroom observation pointed to an activating influence of Org 2766, as revealed by a significant decrease of stereotypic behavior and significant increases in "change toys," "locomote," and "talk." Checklist ratings did not show significant changes. The clinical implications of these findings are discussed.

Adrenocorticotropic Hormone↗

PubMed1988

[Behavioral effects of quinupramine, a new tricyclic antidepressant].

The effects of a new tricyclic antidepressant quinupramine (5-(3-quinuclidinyl)-10,11-dihydro-5H-dibenz [b, f] azepine) on various animal behaviors were examined in mice and rats and compared with those of imipramine, amitriptyline and maprotiline. Quinupramine antagonized haloperidol-induced catalepsy and tetrabenazine-induced ptosis and potentiated methamphetamine- and apomorphine-induced stereotyped behavior. These effects were almost the same as or even more potent than those of imipramine and amitriptyline. Quinupramine decreased locomotor activity in mice, but potentiated methamphetamine-induced hyperactivity to a greater degree than imipramine and amitriptyline. On the other hand, quinupramine inhibited muricide in accumbens-lesioned rats, but did not prominently inhibit muricide in olfactory-bulbectomized and raphe-lesioned rats. Quinupramine decreased the duration of immobility in low doses without affecting locomotor activity, and this effect was almost the same as that of imipramine and amitriptyline and more potent than that of maprotiline. Quinupramine antagonized physostigmine lethality and oxotremorine-induced tremor, suggesting that quinupramine has a central anticholinergic action. Quinupramine, like imipramine and amitriptyline, has no effect on conditioned avoidance behavior. In conclusion, quinupramine generally has the same behavioral profile as typical tricyclic antidepressants, but it has somewhat different effects from imipramine and amitriptyline since quinupramine has a potent central anticholinergic and a weak antimuricide effect.

Animals↗

PubMed1982

Behavioral observation and intracerebral electrochemical recording following administration of amphetamine in rats.

Intracerebral electrochemistry (chronoamperometry) was performed on rats that were administered 1, 4, and 8 mg/kg doses of amphetamine. Graphpoxy working electrodes were implanted bilaterally in nucleus accumbens (ACC) and ventral anterior stratum (VAS). Following drug injection, locomotor and stereotyped behaviors were observed. Intracerebral electrochemical signals reliably increased following injection of amphetamine. The magnitude of these increases did not change significantly across the dose range tested for VAS electrodes. ACC electrodes had increases similar in magnitude to VAS electrodes at 1 and 4 mg/kg. At 8 mg/kg increases obtained from ACC electrodes were significantly lower than those recorded from VAS. Onset of the change in electrochemical signal paralleled the onset of activity or stereotypy but the subsequent declines in signal and behavior were only loosely correlated. At the 4 mg/kg dose, the magnitude of signal increase from striatum was negatively correlated with indices of stereotypy and positively correlated with locomotor counts.

Amphetamine↗

PubMed1985

[Behavioral pharmacology of amantadine with special references to the effect on abnormal behavior in mice and rats].

Behavioral effects of amantadine, especially on abnormal behavior in mice and rats, were reevaluated, in comparison with those of tricyclic antidepressants, methamphetamine and L-DOPA. 1) Amantadine at 10 approximately 50 mg/kg, i.p., tended to decrease ambulation and rearing in rats and mice. The drug at 50 mg/kg, i.p., caused piloerection and hyperirritability and at doses over 80 mg/kg, i.p., it impaired coordinated motor activity in rats. 2) Amantadine inhibited methamphetamine-induced hyperactivity, but apomorphine-induced stereotyped behavior was unaffected in rats. 3) Amantadine was equipotent to imipramine in suppressing haloperidol-induced catalepsy in rats, but L-DOPA was without effect. On the other hand, amantadine was 40 and 400 times as potent as imipramine and L-DOPA, respectively, in suppressing delta 9-tetrahydrocannabinol (THC)-induced catalepsy in rats. 4) Amantadine was as potent as imipramine in suppressing the muricide of olfactory bulbectomized rats, but was 3.5, 8.8 and 225.5 times as potent as methamphetamine, imipramine and L-DOPA, respectively, in inhibiting THC-induced reversible muricide in rats. 5) Amantadine at 50 mg/kg did not elicit circling behavior in the rat with unilateral nigral lesion induced by 6-hydroxydopamine. 6) Amantadine at high doses caused irritable aggression characterized by squealing in rats pretreated with intraventricular 6-hydroxydopamine. The most important characteristic of amantadine is its prominent effect suppressing the THC-induced catalepsy and muricide. This may be a reflection of the feature of amantadine activating the dopaminergic as well as the serotonergic systems.

Aggression↗

PubMed1986

The effect of antimuscarinic agents on haloperidol induced behavioral hypersensitivity.

Varying doses of scopolamine, trihexyphenidyl and benztropine were administered to rats or guinea-pigs by themselves or in combination with 0.5 mg/kg haloperidol for 24 days. All animals were then challenged with 0.75 mg/kg apomorphine and assessed for stereotypic behavior following a 96 h drug free interval. Animals treated with haloperidol alone exhibited behavioral hypersensitivity to apomorphine challenge. Animals treated with both an antimuscarinic agent and haloperidol exhibited a significant reduction in behavioral responsiveness relative to animals treated with only haloperidol. This reduction was directly proportional to the antimuscarinic dose administered. A non-significant trend toward hyposensitivity was observed in animals who had been treated with antimuscarinic agents alone. These results suggest that the development of behavioral hypersensitivity may reflect CNS alterations in cholinergic as well as dopaminergic activity.

Animals↗

PubMed1990

Interactions between imipramine and morphine on motility in rats: possible relation to antidepressant effects?

The aim of the present study was to evaluate whether morphine and the more modern antidepressant drug imipramine have common effects on behavior after both acute and chronic administration, and, in particular, to establish whether they act synergistically. In rats, morphine (15 mg/kg i.p.) produced a pronounced hypokinesia, followed by locomotor activation and stereotyped behavior. After repeated administration (eight times), tolerance to the hypokinesia developed, whereas locomotor activation and stereotypies occurred earlier and were more pronounced. Subacute pretreatment with imipramine (twice daily 10 mg/kg i.p. for eight days) enhanced and prolonged hypokinesia and delayed the manifestation of stereotypies and locomotor activation. In contrast, chronic treatment with imipramine (for 29 days) no longer inhibited morphine-induced stereotypies and locomotor activation, but seemed to enhance them when they were tested in rats repeatedly treated with morphine. When the same rats were tested with morphine (15 mg/kg) seven days after withdrawal of morphine and imipramine, morphine produced increased stereotypies and a slight enhancement of locomotion. The experimental conditions used excluded the possibility that conditioning phenomena might explain the enhancement of (probably dopamine-mediated) behavior. Furthermore, the results demonstrated that 1) acute administration of morphine and subacute administration of imipramine may act in a synergistic way, and 2) repeated administration of morphine and chronic treatment with imipramine also act synergistically, although contrary to the acute actions of both drugs. These interactions might be of therapeutic or toxicological relevance.

Animals↗

PubMed1996

Changes in cholecystokinin mRNA expression in methamphetamine-induced behavioral sensitization.

Neuropeptide cholecystokinin (CCK) mRNA was measured in the rat brain subchronically treated with methamphetamine (MAP). Male Wistar rats were injected daily with MAP (3 or 6 mg/kg, i.p., once a day) or saline for 14 days. Progressive reinforcement was observed in MAP-induced stereotyped behaviors. After 7 or 14 days of discontinuation, the rats were decapitated and the brains were prepared for Northern blot analysis using 32P-labeled cDNA probes. Northern blot analysis revealed that the levels of CCK mRNA in the frontal cortex and the hippocampus of 3 or 6 mg/kg MAP-treated rats were significantly decreased, compared to the saline-treated controls. These findings indicate that the alteration in CCK mRNA levels in the frontal cortex and the hippocampus of MAP-treated rats persisted for at least 2 weeks and might be involved in the expression of MAP-induced long-lasting behavioral sensitization (reverse tolerance).

Animals↗

PubMed1987

Chronic intrastriatal dopamine infusions in rats with unilateral lesions of the substantia nigra.

This study examined the effects of continuously supplied dopamine delivered directly into the dopamine-deficient striatum. Rats received unilateral lesions of the substantia nigra by stereotaxic administration of 6-hydroxydopamine and were tested for apomorphine-induced rotational behavior and general activity. Osmotic mini-pumps were filled with dopamine in various concentrations, implanted subcutaneously and connected to a cannula implanted directly into the striatum. The system delivered solution at a rate of .5 microliter/hr for two weeks. Dopamine in a dosage of 0.5 microgram/per hour reduced apomorphine-induced rotational behavior by a mean of 52 +/- 5.8% (mean +/- SEM, n = 20) with a maximal individual decrease of 99%. There was no change in general activity or increase in stereotyped behavior. Infusions of vehicle solutions did not decrease rotational behavior. Spread of the infused dopamine and its metabolites was estimated by adding 3H-dopamine to the pumps in tracer quantities. Radioactivity was highly concentrated at the infusion site and decreased rapidly within a few mm from the infusion site. Continuous infusion methods may eventually prove to be effective in the treatment of nigro-striatal degenerative disease.

Animals↗