Decreased hyperthermic effect of MK-801 in selectively bred hypercholinergic rats

The Flinders Sensitive Line (FSL) of rats has been selectively bred to have increased sensitivity to cholinergic agonists. However, these rats exhibit altered responsiveness to a number of noncholinergic agents, such as apomorphine, buspirone and ethanol. This study compared the FSL and control Flinders Resistant Line (FRL) rats in terms of their hyperthermic response to the phencyclidine (PCP) receptor agonist, MK-801 (0.2 mg/kg SC) and their MK-801 binding characteristics. We have found that FSL rats react with a delayed hyperthermia, having a significantly lower hyperthermia for the first 120 min of observation. Thereafter the response does not differ in FSL and FRL rats. Both groups had similar affinities and numbers of [3H]MK-801 binding sites in the hippocampus/cerebral cortex. Pretreatment with scopolamine (1 mg/kg SC) failed to affect MK-801-induced hyperthermia in either line of rats. These findings suggest that selective breeding of FSL rats attenuated the secondary mechanisms involved in the PCP receptor-mediated hyperthermic response. However, by itself cholinergic supersensitivity does not appear to be a major factor in the blunted responsiveness of FSL rats to MK-801.     

Chronic oral treatment with diltiazem or verapamil decreases isolation-induced activity impairment in elevated plus maze

Adult male Wistar rats were either socially isolated or group-housed for 6 weeks and then tested in an elevated plus maze. During isolation the rats received either water or two concentrations of the calcium channel inhibitors, diltiazem or verapamil, in drinking solutions (approximately 5 and 10 mg/kg daily). Isolated rats showed a significantly lower total number of arm entries, a lower percentage of open arm entries and negligible time spent therein than did group-housed animals. Verapamil, in the higher dose, prevented that effect of isolation. Treatment with diltiazem brought about a similar tendency, though the effect did not reach statistical significance. Chronic treatment of group-housed rats with either drug failed to influence their behavior in the plus maze. We conclude that certain calcium channel inhibitors may decrease the behavioral deficit in the elevated plus maze that follows chronic social isolation.     

Suppression of alcohol and saccharin preference in rats by a novel Ca2+ channel inhibitor,Goe 5438

The effect of the novel 1,4-dihydronaphthyridine Ca²⁺ channel inhibitor Goe 5438 (CI-951) on voluntary ethanol consumption was examined in selectively bred alcohol-preferring (P) rats in a free choice two bottle preference test versus water. Intraperitoneally injected Goe 5438 dose-dependently (5, 10 or 20 µmol/kg, twice daily) inhibited ethanol and increased water intake over the 24 h period (injection day). The drug decreased ethanol preference, originally above 90%, by 6%, 19% and 45% at respective doses, on the injection day. That inhibitory effect of the highest dose of Goe 5438 on ethanol preference remained significant also on days 2 and 3 after injections (–51% and –18%, respectively). Goe 5438, in the highest dose, also tended to decrease granulated chow consumption during the injection day only. To further test whether the inhibition of ethanol preference is secondary to decrease in reinforcing properties of ethanol and not due to interference with satiety mechanisms, we compared the effect of two higher doses (10 and 20 µmol/kg, intraperitoneally, twice daily) of Goe 5438 on spontaneous preference for a non-caloric 0.04% saccharin solution in Sprague-Dawley rats. We observed a dose-dependent suppression of preference (by 44% and 58%, respectively) during the injection day, but not the subsequent 24 h period. However, Goe 5438 also significantly alleviated food pellet intake on the injection day. In conclusion, Goe 5438 produces potent and long-lasting inhibition of voluntary ethanol consumption, which may be secondary to attenuation of reinforcing properties of ethanol. Additionally, this particular Ca²⁺ channel inhibitor appears to have mild anorectic properties which may be conducive to acute suppression of alcohol intake.     

Administration of antidepressants,diazepam and psychomotor stimulants further confirms the utility of Flinders Sensitive Line rats as an animal model of depression

Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression because they resemble depressed humans in that they have elevated REM sleep, reduced activity, and increased immobility and anhedonia after exposure to stressors. The present paper reviews experiments on the drug treatment of FSL and control Flinders Resistant Line (FRL) rats related to their utility as an animal model of depression, and presents new information. FSL rats exhibited exaggerated immobility in the forced swim test which is counteracted by the tricyclic antidepressants imipramine and desipramine and the serotonin reuptake blocker sertraline; the low immobility exhibited by the FRL rats is generally unaffected by these compounds. In contrast to these therapeutic effects of well recognized antidepressants, lithium and bright light treatment did not alter the exaggerated immobility of FSL rats. Novel data indicated that neither FSL nor FRL rats exhibited alterations in swim test immobility following chronic administration of the psychomotor stimulant amphetamine (2 mg/kg) and the anticholinergic scopolamine (2 mg/kg), which typically reduce immobility after acute administration. However, it was found that the calcium channel blockers verapamil (5 and 15 mg/kg) and nicardipine (10 mg/kg) did reduce the exaggerated immobility in FSL rats following chronic administration, suggesting that these compounds need to be evaluated further in humans. Previous studies have indicated no differences between FSL and FRL rats evaluated in the elevated plus maze, either at baseline or after the administration of diazepam, suggesting that the FSL rat may not differ from controls in anxiety-related behavior. Another recently published study showed that the FSL rat also did not differ from normal Sprague-Dawley rats in startle tests, indicating that the FSL rats do not exhibit behaviors shown in animal models of schizophrenia. These findings confirm the utility of FSL rats as an animal model of depression because the FSL rats do not appear to exhibit behaviors analogous to anxiety or schizophrenia and because they respond therapeutically to antidepressants and not psychomotor stimulants.     

Accumulation of Cadmium in and Its Effect on the Midgut Gland of Terrestrial Snail Helix pomatia L. from Urban Areas in Poland

The objectives of this study were (1) to determine cadmium (Cd) accumulation in the midgut gland of a land snail Helix pomatia L. inhabiting residential areas of the 14 largest cities in Poland, and (2) to examine whether the accumulated Cd exerted any toxic effects. The average accumulation of Cd in the midgut gland of snails, weighing 16–18 g, ranged from 7.00 to 87.3 µg/g dry weight (0.06–0.77 µmol/g) and differed significantly among animals from the various urban areas. This difference in Cd accumulation was not related to city population, but was associated with the topsoil Cd (R² = 0.868, p < 0.0001). The tissue Cd was not found to produce toxicity (histopathology, programmed cell death, lipofuscin formation or lipid peroxidation), probably due to the induction of sufficiently high quantities of metallothionein and glutathione, well-known protective molecules.     

Effect of verapamil on submissive behavior in genetically bred hypercholinergic rats in a water competition test

Male hypercholinergic FSL (Flinders Sensitive Line) and control FRL (Flinders Resistant Line) rats were placed on a water deprivation schedule and tested for dominance behavior with FSL/FRL pairs competing for water. FSL rats spent significantly less time drinking than their FRL partners. Acute injection of 10 mg/kg of verapamil, a calcium channel inhibitor, to FSL rats markedly increased their drinking time without influencing water intake in individually tested rats. This effect of the drug was no longer seen after prolonged 4 day treatment. It is suggested that submissiveness of FSL animals in the water competition test might be due to increased fear which is alleviated by verapamil treatment. Tolerance seems to develop to this effect of the drug.     

Localization and clinical characteristics of the ocular metastases of solid extraocular tumours

Localization and clinical characteristics of the ocular metastases of solid tumours are presented. Choroid is the most common localization site of these metastases, however they may involve each ocular structure. In the most cases they are diagnosed in patients with earlier recognized cancer, but in 12-40% of the patients ocular metastasis is a first sign of the neoplasm. Therapy is focused to save the eye function or last but not least to improve patient's status.     

Enhanced affective aggression in genetically bred hypercholinergic rats

Affective aggression was studied in pairs of Flinders Sensitive Line hypercholinergic rats (FSL) and Flinders Resistant Line (FRL) rats in shock-induced and apomorphine-induced fighting tests. FSL rats were significantly more aggressive in both tests. They had higher pain threshold, assessed by the jump-flinch method, than FRL rats. It is concluded that genetically developed cholinergic system supersensitivity has resulted in enhanced responsiveness to stimuli eliciting affective aggression.