Compensatory nicotine self-administration in rats during reduced access to nicotine: An animal model of smoking reduction.

The ability of smoking reduction (e.g., decreasing cigarettes per day) to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon. The goal of the current study was to develop an animal model of smoking reduction and to begin to examine potential behavioral and pharmacokinetic contributors to compensation. Rats trained for nicotine self-administration (NSA) in unlimited access sessions were exposed to a progressive decrease in duration of access to nicotine from 23-hr/day to 10-, 6-, and 2-hr/day. Following a return to 23 hr/day access and extinction, single-dose nicotine pharmacokinetic parameters were determined. Rats exhibited a reduction in total daily nicotine intake during reduced access to NSA, but decreases in nicotine intake were not proportional to decreases in access duration. Compensatory increases in hourly infusion rate were also observed when access was decreased. The magnitude of compensation differed considerably among animals. Early session infusion rate during baseline was significantly correlated, while nicotine clearance was moderately correlated, with 1 measure of compensation. Infusion rates were transiently increased compared to prereduction levels when unlimited access was restored, and this effect was greatest in animals that had exhibited the greatest levels of compensation. These findings indicate that rats exhibit compensatory increases in NSA during reduced access to nicotine, with substantial individual variability. This model may be useful for characterizing underlying factors and potential consequences of compensatory smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Neurogenically mediated cystitis in rats: an animal model

PURPOSE: Pseudorabies virus (PRV) is a useful tool for mapping the control circuitry of the spinal cord. In the process of mapping CNS regulatory pathways for the lower urinary tract, a hemorrhagic change in the bladder was observed that was not overtly evident in other pelvic organs. The relationship between the appearance of hemorrhagic changes in the bladder and the evolution of PRV induced changes in the spinal cord was therefore explored. MATERIALS AND METHODS: Sprague-Dawley rats were injected with PRV into the ACD tail-muscle. Bladder and CNS fixation were achieved by transcardial perfusion with formaldehyde. Multi-level sections were obtained from T8 through S4. Fixed tissue was stained and evaluated by light microscopy. Immunohistochemical stains were carried out for PRV and iNOS on spinal cord tissue. We were therefore able to evaluate the relationship between the manifestation of the hemorrhagic cystitis, appearance of the PRV in the spinal cord and evidence of CNS inflammation. RESULTS: The evolution of hemorrhagic cystitis paralleled the evidence of inflammation in the thoraco-lumbar and sacral cord. These bladders contained 5 to 9 ml. of bloody urine (a normal rat bladder contains 1 to 2 ml.). On cystomanometry (CMG) the bladders were acontractile. No PRV could be cultured in the hemorrhagic bladders. The histological changes observed in the bladder represent true inflammation. CONCLUSION: There was no obvious explanation for these changes other than the associated inflammatory changes in the spinal cord. The findings are consistent with the hypothesis that a spinal cord stress, via an unknown metabolic pathway, can result in dramatic, neurogenically mediated changes in the bladder.     

Uncontrollability and unpredictability in post-traumatic stress disorder: An animal model.

The disturbances observed in animals subjected to unpredictable and uncontrollable aversive events resemble posttraumatic stress disorder (PTSD) symptoms and thus may constitute an animal model of this disorder. It is argued that the similarity between animals' symptoms and those of trauma victims may reflect common etiological factors. Relevant experiments in which animals exhibit generalized fear and arousal, discrete fear of a CS, analgesia, and avoidance are reviewed with the view that these manifestations may be analogous to the PTSD symptom clusters of persistent arousal, reexperiencing, numbing, and avoidance, respectively. Finally, animal paradigms are suggested to test the validity of the model, and specific hypotheses are derived from the animal literature regarding trauma variables that are predictive of particular PTSD symptom clusters. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brainstem auditory evoked responses in patients with tinnitus

Brainstem auditory evoked responses of 355 patients with uni- or bilateral tinnitus were recorded in order to evaluate the effect of tinnitus on the central auditory system. The amplitudes of waves I, III and V and the latencies of each wave and interpeak latencies were compared to those of a group of 129 controls with normal hearing. The study of the control group initially identified a certain number of concurrent parameters. The brainstem evoked responses of men and women evolved differently from the age of 30 years, latencies of I-III and I-V in men lengthening with age and those of women tending to shorten. The patient groups were therefore compared to a control group of the same sex ratio or of the same sex, half being between 30 and 56 years of age. The tinnitus patients were divided into three groups according to the side affected by tinnitus. Latencies and amplitudes in these groups differed significantly from those of the control group. In order to eliminate hearing loss, the most difficult concurrent factor and almost always associated with tinnitus, the results of individuals with symmetrical hearing loss were compared to those of the control group. Tinnitus was always associated with significant lengthening of 0-I and I-V latencies on the tinnitus-affected side, with a significant reduction in amplitudes of waves I and III, and sometimes of wave V, particularly in the group with left-sided tinnitus. Comparison of tinnitus patients with symmetrical and asymmetrical hearing by sex showed that tinnitus patients of all groups had lengthening of right and left 0-I latencies, apart from the women in the group with right-sided tinnitus, and significant reduction in amplitudes of waves I and III in women and of left III only in men. When hearing loss was asymmetrical and on the tinnitus-affected side, there was also lengthening of 0-I latencies on the tinnitus-affected side in both sexes and of ipsi- and contralateral I-V latencies in women. Right- and left-sided tinnitus was associated with additional differences between the three groups. Correlation coefficient study confirmed that 0-I, I- III and I-V latencies were independent of the mean degree of deafness, deafness at high frequencies and at frequencies around the tinnitus, up to a threshold of hearing loss of 40 dB, above which 0-I and 0-V lengthened in addition to tinnitus. On the other hand, whatever the frequency, tinnitus involved significant lengthening of wave I latencies and modification of the previously recorded amplitudes. Two groups of tinnitus patients could be distinguished: the first, with symmetrical hearing loss, with symmetrical normal latencies, apart from 0-I latencies and the amplitude of the wave on the tinnitus side, and the second with hearing loss predominant on the tinnitus-affected side, with different latencies on each side, 0-I being shorter on the unaffected side, I-III and I-V being lengthened on the unaffected side and 0-I being lengthened on the tinnitus-affected side. Moreover, as disturbances of brainstem evoked responses caused by tinnitus particularly affected waves I and III, the hypothesis of possible involvement of the efferent systems could be proposed.     

Memory impairment in obese Zucker rats: An investigation of cognitive function in an animal model of insulin resistance and obesity.

The genetically obese Zucker rat is a widely investigated model of pathological changes associated with type 2 diabetes. To assess cognitive function, obese and lean Zucker rats were tested on a variable-interval delayed alternation test of learning and memory. There were no group differences in learning the alternation rule or at short intervals, but obese rats were impaired at longer intervals where performance is hippocampus dependent. Plasma membrane association of the insulin sensitive glucose transporter, GLUT4, was reduced in the hippocampus of obese rats in the absence of changes in total GLUT4 and insulin receptor expression. These results parallel those of human studies in pointing to the susceptibility of the hippocampus and related structures to the adverse environment of diabetes mellitus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dysbaric osteonecrosis in divers and caisson workers. An animal model

Dysbaric osteonecrosis was induced successfully in adult sheep after 12 to 13, 24-hour exposures to compressed air (2.6-2.9 atmospheres absolute) during a 2-month period. All exposed sheep had decompression sickness and extensive bone and marrow necrosis in their long bones. Radiographic analysis of these progressive lesions showed mottled to distinct medullary opacities and endosteal thickening characteristic of dysbaric osteonecrosis. Six months after the last hyperbaric exposure, neovascularization of once ischemic fatty marrow was centripetal from the diaphyseal cortex. Proliferating endosteal new bone, fatty marrow calcification, and appositional new bone formation were widespread. Juxtaarticular osteonecrosis involved marrow fibrosis and loss of osteocytes in subchondral cortical bone. Tidemark reduplication in juxtaarticular bone and cartilage thinning suggested possible early osteoarthritis induction by recurrent episodes of transient ischemia after multiple hyperbaric exposures. Dysbaric osteonecrosis appears to involve a bone compartment syndrome of elevated intramedullary pressure initiated by decompression induced N2 bubble formation in the fatty marrow of the long bones. An animal model that can be used to investigate the pathogenesis, diagnosis, and treatment of dysbaric osteonecrosis is discussed.     

An animal model of neuropathic pain: a review

Recent work has succeeded in producing models of painful peripheral neuropathies in laboratory animals. There is evidence that the animals experience both abnormal spontaneous pain and abnormal evoked pains (allodynia and hyperalgesia). Experimental analyses of these models have demonstrated potential pathophysiologic mechanisms in both the peripheral and central nervous systems; it is likely that the model neuropathic pain syndromes are due to several different mechanisms. One line of evidence suggests that these pain states gradually become centralized due to an excitotoxic effect on spinal cord dorsal horn inhibitory interneurons. The role of the sympathetic nervous system appears to vary, depending on the type of nerve injury and the temporal evolution of the syndrome. There is evidence indicating that the abnormality of cutaneous temperature regulation that often accompanies painful peripheral neuropathy is not necessarily due to the activity of sympathetic vasomotor efferents.     

Schizophrenia, infection and temperature. An animal model for investigating their interrelationships

Cell-free supernatants of 40 Salmonella strains of different serovars were tested for the existence of enterotoxic substances in the rabbit skin permeability factor test, rabbit ileal loop test, tissue culture assays (CHO K1, RTG-2), and baby mouse test. There were differences in the test results between the strains even within the same serovar. Correlation coefficients between the results of different toxin tests were low. It is therefore improbable that the "enterotoxic activity" of Salmonella is caused by only one toxic substance. The activities revealed in the different test systems could not be related to virulence or the epizootiological behaviour of the strains. The in vitro occurrence of the virulence factor "enterotoxin production" is lower for Salmonella than for E. coli and V. cholerae.     

Gap detection deficits in rats with tinnitus: A potential novel screening tool.

The study describes a novel method for tinnitus screening in rats by use of gap detection reflex procedures. The authors hypothesized that if a background acoustic signal was qualitatively similar to the rat's tinnitus, poorer detection of a silent gap in the background would be expected. Rats with prior evidence of tinnitus at 10 kHz (n = 14) exhibited significantly worse gap detection than controls (n = 13) when the gap was embedded in a background similar to their tinnitus. No differences between tinnitus and control rats were found with 16 kHz or broadband noise backgrounds, which helped to rule out explanations related to hearing loss or general performance deficits. The results suggest that gap detection reflex procedures might be effective for rapid tinnitus screening in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An animal model of hypoxia-induced perinatal seizures

Clinically, neonatal hypoxic encephalopathy is commonly associated with seizure activity. Here we describe a rodent model of cerebral hypoxia in which there is are age dependent effects of hypoxia, with hypoxia inducing seizure activity in the immature rat, but not in the adult. Global hypoxia (3-4% O2) induced acute seizure activity during a window of development between postnatal day (P5-17), peaking at P10-12. Animals which had been rendered hypoxic between P10-12 had long term decreases in seizure threshold, while animals exposed at younger (P5) or older (P60) ages did not. Antagonists of excitatory amino acid (EAA) transmission appear to be superior to benzodiazepines in suppressing the acute and long term effects of perinatal hypoxia, suggesting involvement of the EAA system in these phenomena. No significant histologic damage occurs in this model, suggesting that functional alterations take place in neurons when exposed to an hypoxic insult at a critical developmental stage. Future work is directed at evaluating molecular and cellular events underlying the permanent increase in seizure susceptibility produced by this model.     

A proposed animal model for hallucinogens based on LSD's effects on patterns of exploration in rats.

Examined the utility of various measures of exploratory activity in rats in an animal model of hallucinogens. A hole board chamber, connected by a door to a home cage, provided 2 test situations. Ss either were placed directly into the hole board with the door closed (forced exploration) or were placed in the home cage and, following adaptation, the door was opened (free exploration). The monitoring system provided both quantitative measures (crossovers, rearings, and hole pokes) and qualitative measures of locomotor patterns. Four experiments, in which 196 male Sprague-Dawley rats received subcutaneous injections of saline or 2–260 μg/kg LSD, revealed 3 major categories of effects, distinguishable on the basis of dose dependency, time course, or response to environmental manipulation: (a) increased avoidance of novel and central areas, (b) disruption of the spatial patterning of locomotion, and (c) suppression of rearing. All 3 effects exhibited partial tolerance 24 hrs after 1 injection of 30 μg/kg LSD and complete tolerance after 5 daily injections. The possibility that LSD's enhancement of neophobia in rats may be a valid analog model of its intensification of affective reactions in humans is discussed. (53 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An animal model for cochlear microcirculatory disorders by photochemically initiated thrombosis

Making an ideal animal model of cochlear microcirculatory disorders is an important method in studying inner ear microcirculation. After intravenous injection of Rose bengal (30 mg/kg), the lateral wall of the cochlea of guinea pigs was illuminated with green light (wavelength: 550 +/- 20 nm). The Rose bengal photoactivatedly produces oxygen radicals and oxygen singlets, which subsequently damage the endotheliocytes to cause adhesion and aggregation of platelets in the small vessels. After the photo-illumination, cochlea blood flow reduced sharply, and CAP amplitude decreased in 10 min and disappeared completely in about 20-40 min. With prolongation of time, stria vascularis, Corti's organ and spiral ganglion cells showed further disintegration due to ischemia, which resembled the histopathological changes of the cochlea with microcirculatory disorders. Therefore, this animal model may be considered an ideal one for studying the mechanisms of hearing loss that was caused by microcirculatory disorders and also for evaluating the effects of drugs on microcirculation of damaged cochlea.     

An intraventricular infusion model for inducing morphine dependence in rats: Quantitative assessment of precipitated withdrawal.

Describes an experimental model of morphine dependence in which male Sprague-Dawley rats were made dependent upon morphine by intraventricular infusion. Morphine dependence was quantified by a series of withdrawal signs that were induced by the intraperitoneal administration of the morphine antagonist naloxone (5 mg/kg). The infusion of different concentrations of morphine resulted in the production of physical dependence, the severity of which was directly correlated with the concentration of morphine infused. A weak to moderate degree of dependence characterized by such withdrawal signs as teeth chattering, whole-body shakes, and vocalization was produced by infusions of morphine less than 5 μg/hr. A strong degree of physical dependence characterized by additional dominant withdrawal signs such as jumping and launching was produced by the infusion of 50 μg/hr morphine. The morphine pellet model that most closely approximated this degree of dependence was a 3-pellet model in which a single 75-mg morphine pellet was implanted at 48-hr intervals. Abstinence precipitated by removal of the morphine-containing osmotic minipumps was characterized primarily by teeth chattering and whole-body shakes that persisted for at least 48 hrs. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An auditory illusion predicted from a weighted cross-correlation model of binaural interaction.

In humans, the lateral movement of an acoustic source produces dynamic changes in the relative sound-pressure level and time of arrival of the acoustic wave at the 2 ears. The dynamic nature of these cues is assumed to play an important role in the perception of lateral motion. A phenomenon of auditory motion is reported whose lateral direction and relative velocity may be specified while interaural differences are kept constant. The stimulus producing this percept is a narrowband waveform whose instantaneous bandwidth is a cosine function of time. This phenomenon is predicted from a model of cross-correlation that estimates the running position of an image from a weighted combination of 2 variables: (a) magnitude of interaural delay, with smaller delays receiving more weight, and (b) consistency of interaural information across frequency. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An auditory localization model based on high-frequency spectral cues

We present in this paper a connectionist model that extracts interaural intensity differences (IID) from head-related transfer functions (HRTF) in the form of spectral cues to localize broadband high-frequency auditory stimuli, in both azimuth and elevation. A novel discriminative matching measure (DMM) is defined and optimized to characterize matching this IID spectrum. The optimal DMM approach and a novel back-propagation-based fuzzy model of localization are shown to be capable of localizing sources in azimuth, using only spectral IID cues. The fuzzy neural network model is extended to include localization in elevation. The use of training data with additive noise provides robustness to input errors. Outputs are modeled as two-dimensional Gaussians that act as membership functions for the fuzzy sets of sound locations. Error back-propagation is used to train the network to correlate input patterns and the desired output patterns. The fuzzy outputs are used to estimate the location of the source by detecting Gaussians using the max-energy paradigm. The proposed model shows that HRTF-based spectral IID patterns can provide sufficient information for extracting localization cues using a connectionist paradigm. Successful recognition in the presence of additive noise in the inputs indicates that the computational framework of this model is robust to errors made in estimating the IID patterns. The localization errors for such noisy patterns at various elevations and azimuths are compared and found to be within limits of localization blurs observed in humans.     

Functional lateralization for auditory temporal processing in male and female rats.

In 3 studies, adult male rats showed significantly better discrimination of tone sequences with the right ear than with the left ear. This result parallels similar findings of left-hemisphere specialization for auditory temporal processing in humans and nonhuman primates. Furthermore, because clinical evidence supports a link between specialization of the left hemisphere for auditory temporal processing and for speech processing, these results may reflect evolutionary precursors to left-hemisphere language specialization. Because male rats showed a stronger ear advantage than female rats, the findings may relate to evidence of a stronger right ear advantage in men than in women. Finally, results suggest that neonatal handling enhances lateralization for auditory temporal processing in both sexes. Combined results implicate neuroendocrine mechanisms as important factors in the development of lateralization for auditory temporal processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An animal model of leukemogenesis using transgenic mice

The bcr/abl chimeric oncoprotein is considered to be implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. To investigate its biological function and the role in leukemogenesis in vivo, we generated transgenic mice expressing p210bcr/abl driven by the metallothionein promoter. Two of six founder mice and the transgenic progeny of one leukemic founder mouse developed leukemias several months after birth. Phenotypically, each leukemic mouse showed a thymic enlargement, a marked splenomegaly, and/or lymphnode swellings. Pathological examination revealed that leukemic cells were infiltrated in all tissues examined, especially in thymus, spleen, liver, and lymphnode. Expression of the p210bcr/abl transgene product and increased phosphorylation of cellular proteins in leukemic tissues were detected by the Western blot analysis. In addition, the expressed p210bcr/abl protein was demonstrated to possess an enhanced kinase activity by the in vitro immunecomplex kinase assay. These results indicate that hematopoietic precursor cells expressing the p210bcr/abl transgene product acquired a proliferative advantage and eventually developed leukemias in transgenic mice. The p210bcr/abl transgenic mice are considered to be an excellent animal model to investigate p210bcr/abl function and its role in leukemogenesis in vivo.     

Photodynamic therapy using m-tetra(hydroxyphenyl) chlorin. An animal model

OBJECTIVE: To evaluate the potent photosensitizer m-tetra (hydroxyphenyl) chlorin (m-THPC) by using rabbits with cottontail rabbit papillomavirus-induced tumors and the canine larynx as model systems. DESIGN: Nonrandomized control trial. SETTING: Division of ear, nose, and throat research at a tertiary care teaching hospital. MATERIALS: Rabbits were used for relative retention ratio studies and tissue tolerance tests. Studies on the swelling of normal tissues in the larynx after photoactivation were done with canines. INTERVENTION: Animals were injected with 0.3 mg/kg of m-THPC. At varying intervals, tissues were exposed to 652 nm of light. OUTCOME MEASURES: Outcome measures consisted of four elements: (1) decay of plasma concentration over time, (2) interval to and duration of maximal ratio between drug concentration in normal tissue and tumor, (3) maximal permissible light exposure to normal tissue (skin and laryngeal mucosa) at an optimal interval, and (4) efficacy--number of tumors with partial and complete response. RESULTS: The largest papilloma to skin ratio (10:1) occurred 4 to 8 days after drug injection. The rabbit skin damage threshold was 40 to 60 J/cm2 at 6 days. The canine laryngeal edema and erythema thresholds were 50 to 70 J. A 75% cure rate of papillomas was achieved with tumors that were less than 100 mm2 in area at light doses that ranged from 25 to 75 J/cm2. CONCLUSIONS: m-THPC shows efficacy in treating papilloma virus-induced tumors. We present a protocol for rapid optimization of the factors required for tumor destruction with minimal normal tissue damage, thus permitting determination of an optimal therapeutic protocol for any photosensitizer.