An animal behavior model for studying the actions of LSD and related hallucinogens

Cats injected with LSD (d-lysergic acid diethylamide) exhibit a group of behaviors that appear to be specific to hallucinogenic drugs. Two of these behaviors, limb flick and abortive grooming, have an extremely low frequency of occurrence in normal cats, but often dominate the behavior of LSD-treated cats. The frequency of occurrence of this group of behaviors is related to the dose of LSD. The behavioral changes are long-lasting following a single injection of LSD, and exhibit tolerance following the repeated administration of LSD. They are not elicited by a variety of control drugs, but are elicited by other indole nucleus hallucinogens. Because the behavioral effects are specific, reliable, easy to score, and quantifiable, they represent an animal model that can be used in studies of the effects of LSD and related hallucinogens.     

Pharmacological and behavioral components of tolerance to LSD and mescaline in rats

A fixed-ratio schedule of water reinforcement (FR-10) was used to examine the relative contributions of pharmacological and behavioral mechanisms in the development of tolerance to the disruptive effects of LSD and mescaline in the rat. Rats treated daily with LSD or mescaline before operant testing developed tolerance to the impairement of responding, while rats treated daily after each session did not display tolerance when the drugs were administered before testing. These results indicate that behavioral compensatory mechanisms may be involved in the development of tolerance to the disruptive effects of LSD and mescaline on fixed-ratio (FR-10) performance.     

An animal model for the behavioral effects of interferon.

Interferon, which is produced during viral infections, has cognitive and neurological effects in humans. A dose of 1600 U/g of mouse interferon-alpha significantly depressed horizontal activity, head pokes into a food chamber, and food intake in mice 10 hr and 24 hr after injection. An 800 U/g dose had only slight effects on horizontal activity and food intake, whereas a 400 U/g dose had no effect. There was no evidence of sensitization to interferon when a second 400 U/g dose was given after the 1600 U/g dose. The results imply that mouse interferon-alpha can be used in mice as a model for studying the fatigue and anorexia produced by interferon. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Collagen VI deficiency induces early onset myopathy in the mouse: an animal model for Bethlem myopathy

To gain insight into the function of type VI collagen, the col6a1 gene was inactivated by targeted gene disruption in the mouse. The homozygous mutants lacked collagen VI in the tissues and showed histological features of myopathy such as fiber necrosis and phagocytosis and a pronounced variation in the fiber diameter. Muscles also showed signs of stimulated regeneration of fibers. Necrotic fibers were particularly frequent in the diaphragm at all ages examined. Similar, although milder, alterations were detected in heterozygous mutant mice, indicating haploinsufficiency of the col6a1 gene function. The data led us to conclude that collagen VI is necessary for maintenance of the integrity of muscle fibers and that the col6a1 -deficient mouse can be considered an animal model of Bethlem myopathy.     

Neurochemical and behavioral factors in the development of tolerance to anorectics.

Four tests, with 60 male Sprague-Dawley rats, investigated tolerance and cross-tolerance among several anorectic drugs. In the 1st test, Ss given milk shortly after intraperitoneal injection of 3 mg/kg dextroamphetamine sulfate (controls) developed tolerance to amphetamine anorexia, but Ss given milk when amphetamine's anorectic effects had worn off (experimental Ss) did not develop tolerance in spite of equal drug exposure. In the 2nd test, controls were tolerant to 2 mg/kg apomorphine HCL, a drug with a neurochemical action related to amphetamine. No tolerance to 2 mg/kg apomorphine was shown by experimental Ss. Both groups were tolerant to 1.25 mg/kg apomorphine. The final test replicated part of the 1st test, demonstrating that the control group was tolerant to amphetamine but the experimental group was not. In addition, neither group was tolerant to anorexia produced by 5 mg/kg fenfluramine, a drug whose action is neurochemically different from amphetamine and apomorphine. It appears that both learning and specific neurochemical mechanisms are involved in the development of tolerance to anorectic drugs. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhaled dry-powder formoterol and salmeterol in asthmatic patients: onset of action, duration of effect and potency

Salmeterol and formoterol are two long-acting beta2-agonists for inhalation, currently being used in clinical practice. The aim of the present study was to investigate the onset of action, duration of effect and potency of these two beta2-agonists in asthmatic patients. Patients (n=28) were included on the basis of salbutamol stepwise reversibility (100, 100 and 200 microg, given cumulatively; total reversibility > or =15%). In a double-blind placebo-controlled crossover study, the bronchodilating properties of formoterol 6, 12 and 24 microg were compared with the effects of salmeterol 50 microg. Formoterol was given via Turbuhaler and salmeterol via Diskhaler, and forced expiratory volume in one second (FEV1) was monitored during 12 h. Formoterol at all doses had a more rapid onset than salmeterol as judged from bronchodilation at 3 min after the dose. Formoterol at all doses had a similar duration of effect to salmeterol 50 microg, as judged from bronchodilation at 12 h after dose administration. When the relative potency of the two drugs was compared, salmeterol 50 microg was estimated to correspond to formoterol 9 microg (95% confidence interval: 3-19 microg). We confirm that formoterol and salmeterol are both long-acting beta2-agonists, but with some differences in effect profile. We confirm the more rapid onset of action of formoterol compared with salmeterol, and furthermore, no difference in duration of effect is evident.     

alpha-Cell neogenesis in an animal model of IDDM

Currently there is debate regarding the capacity of pancreatic islets to regenerate in adult animals. Because pancreatic endocrine cells are thought to arise from duct cells, we examined the pancreatic ductal epithelium of the diabetic NOD mouse for evidence of islet neogenesis. We have evidence of duct proliferation as well as ductal cell differentiation, as suggested by bromodeoxyuridine-labeling and the presence of glucagon-containing cells within these ducts. In addition, the ductal epithelia in diabetic NOD mice expressed the neuroendocrine markers neuropeptide Y and tyrosine hydroxylase. These ducts also expressed the homeobox gene product, insulin promoter factor 1. Ductal cell proliferation and expression of these markers was not observed in transgenic NOD mice (NOD-E), which do not develop clinical or histopathological symptoms of IDDM. This suggests that the observed ductal cell proliferation and differentiation was a direct result of beta-cell destruction and insulin insufficiency in these adult diabetic mice, which further suggests that these events are recapitulating islet ontogeny observed during embryogenesis. It is possible that comparable processes occur in the human diabetic pancreas.     

Natural and induced tolerance in an immune network model

It has been proposed that the immune system can be partitioned into central and peripheral immune systems. Recently, Carneiro et al. (1996a, b) proposed a network, model incorporating B and T lymphocytes that explicitly accounts for that partition. This model however, had some limitations that are tackled here. Two main changes were introduced: the average idiotypic connectivity is now an explicit function of time based on empirical evidence; and the activation of T lymphocytes by antigen is described by a log-bell shaped dose response curve. The new model, which also accounts for the CIS and PIS distinction, shows more reasonable results since the frequencies of tolerant, immune or autoimmune responses to an antigen are now correct. The model provides a new interpretation for tolerance induction during the neonatal period, and for the adult tolerance by low or high doses of antigen. It predicts that natural tolerance for antigens available during the neonatal period can be kept indefinitely upon their removal, while tolerance induced in the adult stages is rapidly lost upon transient removal of the antigen. A semiquantitative analysis of the model provides a simple explanation for the different results in terms of the frequency at which a limited set of canonical connectivity structures emerge during ontogenesis.     

Relation of age at onset to duration of episode in unipolar depression.

On the basis of elevated scores on the Center for Epidemiologic Studies Depression Scale, 2,020 persons were selected from a larger community sample to be interviewed and diagnosed using the Schedule for Affective Disorders and Schizophrenia and the Research Diagnostic Criteria procedures. 865 Ss (aged 18–88 yrs) had a history of one or more episodes of unipolar depression. The potential effects of the following variables (singly and in interaction) on duration of episode were assessed by means of multiway frequency table analysis and chi-square: age at onset, sex of S, interval since occurrence of the episode, and type of disorder (major vs minor depressive disorder). The hypothesis that duration of episodes of depression increases with age at onset was not supported. Women, who formed 73.5% of the sample, were more likely to have multiple episodes but did not have longer-lasting episodes. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Child abuse and neglect: Usefulness of the animal data.

This article reviews and critically discusses the relevance of animal data to research on child abuse and neglect. Although parental investment theory can be useful in investigating the adaptiveness, if any, of child abuse and neglect, the evolutionary approach also has some limitations. The most suitable animal models for investigating the psychosocial processes underlying child abuse and neglect are probably found among the nonhuman primates. Whereas the heuristic value of social deprivation paradigms may be limited, recent studies suggest that the spontaneous occurrence of infant maltreatment in monkeys may be the closest approximation to child maltreatment provided by nonhuman animals. The investigation of adaptive and maladaptive processes in the parenting behavior of socially living nonhuman primates can inform research on child abuse and neglect and allow investigators to conduct studies that would be difficult or impossible in humans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Periosteal migration in the growing mandible: an animal model

Migration of mandibular periosteum and attached musculature was tracked along the inferior border of the ramus in growing and nongrowing guinea pigs (Cavia porcellus) over a 6-week period. Particulate metallic growth-tracing implants were placed through the bony mandible and adjacent musculature at two anteroposterior locations and two bony reference markers were placed anteriorly. Quantification from weekly radiographs of growing animals showed marked posterior migration of the periosteum, whereas in nongrowing animals there was negligible periosteum movement. Significantly greater migration occurred in posterior (6.37 +/- 0.76 mm) implants relative to the anterior implants (3.45 +/- 0.86 mm, p < 0.001). The neutral zone, where little periosteal migration occurs, was calculated to be approximately at the anteroposterior center of the molar tooth row. Analysis of the orientation of the medial pterygoid muscle relative to the mandible showed that muscle fibers on average become more horizontal. Thus, the study found differential anteroposterior migration of the mandibular periosteum in growing animals and correlative changes in orientation of the medial pterygoid muscle.     

Increased vulnerability to 3-nitropropionic acid in an animal model of Huntington's disease

There is substantial evidence for both metabolic dysfunction and oxidative damage in Huntington's disease (HD). In the present study, we used in vivo microdialysis to measure the conversion of 4-hydroxybenzoic acid to 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of hydroxyl radical production in a transgenic mouse model of HD, as well as in littermate controls. The conversion of 4-hydroxybenzoic acid to 3,4-DHBA was unchanged in the striatum of transgenic HD mice at baseline. Following administration of the mitochondrial toxin 3-nitropropionic acid (3-NP), there were significant increases in 3,4-DHBA generation in both control and transgenic HD mice, and the increases in the transgenic HD mice were significantly greater than those in controls. Furthermore, administration of 3-NP produced significantly larger striatal lesions in transgenic HD mice than in littermate controls. The present results show increased sensitivity to the mitochondrial toxin 3-NP in transgenic HD mice, which suggests metabolic dysfunction in this mouse model of HD.     

Adrenal medulla graft induced recovery of function in an animal model of Parkinson's disease: Possible mechanisms of action.

Reviews evidence suggesting at least 3 fundamental processes that may underlie the functional effects of adrenal medulla grafts. These include (1) increased permeability of the blood-brain barrier to dopamine (DA); (2) increased serum DA concentrations; and (3) changes in extracellular concentrations of DA and dihydroxyphenylacetic acid in the host brain resulting in a restoration of symmetry in the striatal DA system. Five hypotheses are proposed to explain the behavioral effects of adrenal medulla grafts in light of these processes. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Etiological role of cadmium in hypertension in an animal model

Dahl hypertension-resistant (R) and hypertension-sensitive (S) lines of rats were used to determine whether cadmium plays an etiological role in hypertension. In Study I, weanling (3-week-old) R and S rats of both sexes were given a low-salt (0.4% NaCl) diet and were divided into two groups. Rats in the cadmium group were injected with cadmium (2 mg/kg body weight, ip), whereas the controls received identical volumes of saline. Three weeks after the first injection, no elevations of systolic blood pressure were detected. A second dose of cadmium (1 mg/kg) produced hypertension in S females but not in S males or in R rats of either sex. Also, female S cadmium rats manifested significant (p less than 0.01) mild to moderate renal vascular changes. The concentrations of cadmium in hepatic and renal tissues of S cadmium rats were significantly higher (p less than 0.001) than in R rats. In Study II, weanling (3-week-old) female S rats on a high-salt (4% NaCl) diet were given cadmium (2 mg/kg body weight, ip) at week 3 followed by second and third injections of cadmium (1 mg/kg) at weeks 6 and 23. S controls received the same volumes of saline. Cadmium enhanced the rate and the degree of salt-induced hypertension development. Pathological lesions of periarteritis nodosa in the mesenteric arteries and renal vascular lesions occurred to the same extent in the cadmium and control groups. These data indicate that differences in genetic background influence the development of cadmium-induced hypertension in weanling rats, and that cadmium exacerbates the severity of salt-induced hypertension.     

Histopathologic study of esophageal atresia and tracheoesophageal fistula in an animal model

Authors propose one study of retinal cells population in different stages of ontogenesis and one study of the pigmentogenesis process at the level of uveal tract and external retinal stratum. The study was achieved with embryonic and fetal technique of paraffin inclusion. Concomitantly with loading with pigment of the external retinal stratum and so pigmentary uveal tract is present. Dynamics of the retinol cells population varies with stages and chronological age, the number of pigmented uveal cells increasing proportionally but at different parameters with the pigmented retinal stratum one simultaneous with age under influence specially of humoral factors.     

Nebulisation of surfactants in an animal model of neonatal respiratory distress

AIMS: To evaluate pulmonary deposition and gas exchange following nebulisation of two surfactants by either a jet or an ultrasonic nebuliser. METHOD: After bronchoalveolar lavage (BAL), 19 rabbits were ventilated in four groups. Group A1 (n = 5) and A2 (n = 6) received Technetium-99m labelled Exosurf, and groups B1 (n = 4) and B2 (n = 4) received radiolabelled Survanta. Groups A1 and B1 received jet nebuliser therapy, whereas groups A2 and B2 received ultrasonic nebuliser. Pulmonary deposition, distribution, and blood gases were determined. RESULTS: Pulmonary deposition as per cent of initial dose and mg lipid) was 0.28(0.10)% or 0.59(0.21) mg in group A1, 1.05(0.23)% or 2.21(0.48) mg in group A2, 0.08(0.02)% or 0.30(0.08) mg in group B1, and 0.09(0.02)% or 0.34(0.08) mg in group B2. Deposition in group A2 was greater than in other groups (p = 0.001). Group A2 showed a small improvement in blood gases. CONCLUSIONS: Even the highest deposition--ultrasonic nebuliser with Exosurf--achieved limited clinical effect. The aerosol route is currently not effective for surfactant treatment.     

Bleeding due to needle biopsy: effect of venopirin in an animal model and implications for humans

PURPOSE: This study was undertaken to address the effect of platelet dysfunction on bleeding associated with percutaneous needle biopsy. MATERIALS AND METHODS: With use of an established animal model, 199 biopsies were performed on the livers of 13 anesthetized pigs (95 on control animals, 104 on venopirin-treated animals). The needles used were 16-22-gauge Chiba type, 18-gauge Tru-Cut, and 18-gauge Menghini. The biopsies were performed under direct vision at laparotomy with consistent technique. Blood loss was measured, and the results were compared. Statistical analysis was performed with the Student t test and the Turkey test, after logarithmic transformation of the data. RESULTS: A substantial increase in blood loss resulting from the biopsy procedures was demonstrated in the animals with platelet dysfunction. This was much greater than the effect of either needle size or prothrombin time prolongation previously reported by the authors. CONCLUSION: Platelet function may be an important factor in determining the risk of bleeding due to percutaneous needle biopsy.     

The action of chlorpromazine on the electrodermal response in the cat

Fourty one vulvectomy operation specimens and seventeen biopsies from the vulva were examined. They represented either dysplasias, carcinomata in situ or invasive squamous cell carcinoma. Slightly more than a third of the cases showed early stromal invasion as well in dysplasias and carcinomata in situ as in the margins of the invasive carcinomas. On the other hand the early stromal invasion of the vulva doesn't show that striking alterations as does that of the cervix uteri.     

The canine as an animal model of human aging and dementia

Cytochemical defects in chromatin were examined by transmission electron microscopy (TEM) after the staining by alcoholic phosphotungstic acid (PTA) of normal and malformed ejaculated spermatozoa from 35 male partners of infertile couples, and in six sperm samples retrieved from the caput epididymidis of men affected by obstructive azoospermia. PTA staining was also analysed in normal ejaculates of fertile men after incubation of the washed spermatozoa with dithiothreitol (DTT) to reduce disulfides to thiols, or with DTT followed by iodoacetamide, a blocking agent for thiol groups. PTA stained 63 (27-100)% of malformed heads and 25 (10-100)% of normal sperm heads (median (range) n = 35; P = 0.0001, Wilcoxon matched pairs test). The percentage of normal heads stained by PTA was negatively correlated with the percentage of heads of normal form, with condensed chromatin and a normal acrosome (Spearman r = 0.75; P = 0.0001), and positively correlated with the percentage of malformed heads after conventional TEM analysis (Spearman r 0.60; P = 0.0001). Staining with PTA in normal heads was not correlated with the presence of non-condensed chromatin in otherwise normal sperm heads evaluated by conventional TEM analysis. In spermatozoa recovered from the caput epididymidis, 15% of normal heads were stained with PTA, significantly fewer than in ejaculated sperm samples (P = 0.014). The reduction of disulfides to thiols was associated with PTA staining of all normal heads, and this was prevented by incubation with iodoacetamide. We conclude that PTA staining of the nuclei of human ejaculated spermatozoa may indicate a defect of chromatin condensation, owing to an excess of free thiol groups. The lower percentage of normal epididymal sperm heads that stained with PTA in cases of obstructive azoospermia compared with ejaculated sperm may be related to an overoxidation of thils owing to the ageing of spermatozoa.