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  • 1
    Electronic Resource
    Electronic Resource
    Genetic and pharmacological models of cholinergic supersensitivity and affective disorders (1988)
    Springer
    Cellular and molecular life sciences 44 (1988), S. 465-472 
    Details
    ISSN: 1420-9071
    Keywords: Acetylcholine ; supersensitivity ; depression ; Flinders sensitive and resistant lines of rats ; animal model ; genetic selection ; DFP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Increased muscarinic sensitivity has been associated with altered hormonal states (hypothyroidism and hyperadrenocorticism), chronic administration of muscarinic antagonists or antidepressants with muscarinic actions, selective breeding for anticholinesterase sensitivity, and certain inbred strains of rats and mice. Thus, both genetic and environmental factors may influence muscarinic receptor sensitivity. The reasonably detailed studies on the selectively-bred rats have revealed that the Flinders Sensitive Line (FSL) rats weigh less, are less active, are more sensitive to muscarinic agonists and to stressors, and have higher concentrations of hippocampal and striatal muscarinic receptors than ‘normal’, or the selectively-bred, Flinders Resistant Line (FRL) rats. Thus, there are a number of parallels between FSL rats and depressed humans. The FSL rats may be the first animal model of depression to mimic the actual trait of depression, and not just the state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01958920
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  • 2
    Electronic Resource
    Electronic Resource
    Are there 2 cholinergic thermoregulatory centres in rats? (1977)
    Springer
    Cellular and molecular life sciences 33 (1977), S. 1463-1464 
    Details
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An attempt was made to replicate the conflicting previous reports of hypo- and hyperthermic effects of intrahypothalamically administered carbachol. Despite using the same coordinates, injection parameters, and strain of rats reported by others, only hypothermia was conclusively demonstrated. It was concluded that the cholinergic system mediates heat loss mechanisms in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01918809
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  • 3
    Electronic Resource
    Electronic Resource
    Facilitation of active avoidance responding following chronic haloperidol treatment in rats (1982)
    Springer
    Psychopharmacology 78 (1982), S. 135-136 
    Details
    ISSN: 1432-2072
    Keywords: Haloperidol ; Withdrawal ; Spontaneous locomotor activity ; Active avoidance responding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were chronically treated with once-daily injections of either haloperidol or vehicle for 21 days. When spontaneous locomotor activity or acquisition of active avoidance in a two-way shuttle box were measured 48 h after the cessation of chronic treatment, the haloperidol-treated animals were significantly more active and performed significantly more avoidance responses. These findings suggest that the increased dopamine receptors that have been reported following chronic haloperidol treatment may have functional relevance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432250
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  • 4
    Electronic Resource
    Electronic Resource
    Selective breeding for diisopropyl fluorophosphate-sensitivity: Behavioural effects of cholinergic agonists and antagonists (1982)
    Springer
    Psychopharmacology 78 (1982), S. 150-155 
    Details
    ISSN: 1432-2072
    Keywords: DFP sensitivity ; Selective breeding ; Pilocarpine ; Physostigmine ; Atropine ; Scopolamine ; Locomotor activity ; Operant responding ; Temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioral effects of cholinergic agonists and antagonists were examined in two lines of rats which have been developed through selective breeding techniques to be differentially sensitive to the anticholinesterase diisopropyl fluorophosphate (DFP). The line of rats which were determined to be more sensitive to DFP (Flinders S line) were also more sensitive to the depressant effects of the agonists pilocarpine and physostigmine on locomotor activity, water intake, and operant responding maintained by water reward. In contrast, the locomotor stimulant effects of scopolamine, a muscarinic antagonist, were less marked in the S-line rats, while the depressant effects of atropine and scopolamine on water intake and operant responding maintained by water reward were comparable in the two lines. The S-line rats were also significantly more sensitive to the hypothermic effects of pilocarpine and oxotremorine. These findings are consistent with the hypothesis that the S-line rats are more sensitive to the acute effects of DFP because they have a higher number of muscarinic-cholinergic receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432254
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  • 5
    Electronic Resource
    Electronic Resource
    Modification of the behavioural effects of haloperidol and of dopamine receptor regulation by altered thyroid status (1983)
    Springer
    Psychopharmacology 82 (1983), S. 102-106 
    Details
    ISSN: 1432-2072
    Keywords: Hyperthyroid ; Thyroxine ; Hypothyroid ; Propylthiouracil ; Haloperidol ; Locomotor activity ; Catalepsy ; Dopamine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats made hypothyroid by the chronic oral administration of 200 mg/kg propylthiouracil were less sensitive to the cataleptic effects of haloperidol (0.1 mg/kg) treatment than were euthyroid rats chronically treated with isotonic saline. However, rats made hyperthyroid by the chronic injection of 200 μg/kg thyroxine were not more sensitive to the cataleptic suppressant effects of haloperidol (0.1 mg/kg). Higher doses of haloperidol (1 and 5 mg/kg) produced significantly greater catalepsy in the hyperthyroid rats and significantly reduced catalepsy in the hypothyroid rats. Receptor binding studies carried out on the striata from rats sacrificed 48 h after a 6-day course of chronic haloperidol (0.1 mg/kg once daily) treatment revealed a significant upregulation (increase) of dopamine receptors in the hypothyroid rats only. These findings are consistent with the hypothesis that altered thyroid status can modify the sensitivity of dopamine receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00426390
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  • 6
    Electronic Resource
    Electronic Resource
    Genetic/environment interactions in chronic mild stress (1997)
    Springer
    Psychopharmacology 134 (1997), S. 359-360 
    Details
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050468
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    Paper (German National Licenses)
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  • 7
    Electronic Resource
    Electronic Resource
    Sex differences following pharmacological manipulation of the cholinergic system by DFP and philocarpine (1979)
    Springer
    Psychopharmacology 61 (1979), S. 49-58 
    Details
    ISSN: 1432-2072
    Keywords: DFP ; Pilocarpine ; Sex differences ; Water intake ; Body temperatures ; Serum cholinesterase ; Brain acetylcholinesterase ; Isoenzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of seven experiments was designed to investigate the mechanism(s) responsible for sex differences in the effects of DFP, an irreversible anticholinesterase, on behavioural and physiological variables. It was found that female (Sprague-Dawley) rats were more resistant than males to the effects of DFP: decreases in body temperature and water intake were significantly less in the females. These effects were related to less inhibition of brain acetylcholinesterase (AChE) in female than in male animals. Of the five isoenzymes of AChE separated from homogenates of brain, one was relatively insensitive to the effects of DFP, but all were inhibited to a greater extent in male animals. In contrast to the effects of DFP, female rats were more sensitive to the hypothermic effects of pilocarpine, a directly acting muscarinic agonist, indicating that the resistance of females to the hypothermic effects of DFP could not be attributed to decreased sensitivity of muscarinic cholinergic receptors. Measurement of the degree of radioactivity in brain homogenates following the peripheral administration of {P32}-DFP indicated that the uptake of DFP into the brain was less for female than for male rats. A final experiment confirmed that the females had higher baseline levels of serum cholinesterase activity. It was also found that DFP produced a greater degree of inhibition of this enzyme in females. These experiments suggest that female rats may be less sensitive to the effects of DFP because they have higher levels of serum cholinesterase, which can bind to DFP administered peripherally and reduce the amount available for penetration into the brain. The results also support the hypothesis that the behavioural and physiological effects of DFP are related to the anticholinesterase properties of the agent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00426810
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  • 8
    Electronic Resource
    Electronic Resource
    The influence of ovariectomy on the sex-dependent effects of the anticholinesterase diisopropyl fluorophosphate (1981)
    Springer
    Psychopharmacology 74 (1981), S. 391-392 
    Details
    ISSN: 1432-2072
    Keywords: DFP ; Anticholinesterase ; Sex differences ; Ovariectomy ; Serum cholinesterase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Temperature and water intake were reduced to a greater degree in overiectomized female and normal male rats than in sham-operated female rats following an acute administration of 1 mg/kg of the anticholinesterase diisopropyl fluorophosphate (DFP). Ovariectomy also led to a significant reduction in the level of serum cholinesterase activity. These findings add further support for the hypothesis that the sex-dependent effects of DFP are due, at least in part, to sex differences in serum cholinesterase activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432755
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  • 9
    Electronic Resource
    Electronic Resource
    Evidence for parallel development of tolerance to the hyperactivating and discoordinating effects of ethanol (1977)
    Springer
    Psychopharmacology 55 (1977), S. 75-81 
    Details
    ISSN: 1432-2072
    Keywords: Chronic ethanol treatment ; Locomotor activity ; Rotarod ; Tolerance development ; Chlorpromazine ; Amphetamine ; Propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats maintained on diets containing 6.5% ethanol or equicaloric sucrose solutions were challenged at weekly intervals with 1.5 or 2.0 g/kg ethanol or isotonic saline 14 h after withdrawal from the diet. Tolerance developed to both the hyperactivating (increased line crossing and time active) and discoordinating (disrupted rotarod performance) effects of the 1.5 g/kg dose of ethanol, but was less obvious with the 2.0 g/kg dose. Chlorpromazine (2.5 mg/kg) had a greater depressant effect in animals chronically treated with ethanol, suggesting that some alterations in the functioning of noradrenergic and/or dopaminergic systems may accompany chronic ethanol treatment. However, amphetamine and propranolol did not appear to affect ethanol-and sucrose-treated rats differently. The present studies have therefore shown a parallel development of tolerance to the discoordinating and hyperactivating effects of ethanol and have implicated an underlying noradrenergic and/or dopaminergic mechanism, although the precise nature of the mechanism has not been clarified.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432820
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  • 10
    Electronic Resource
    Electronic Resource
    Administration of antidepressants, diazepam and psychomotor stimulants further confirms the utility of Flinders Sensitive Line rats as an animal model of depression (1995)
    Springer
    Psychopharmacology 121 (1995), S. 27-37 
    Details
    ISSN: 1432-2072
    Keywords: FSL and FRL rats ; Animal model of depression ; Imipramine ; Desipramine ; Sertraline ; Diazepam ; Scopolamine ; Amphetamine ; Nicardipine ; Verapamil ; Immobility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245589
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