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  • 1
    Electronic Resource
    Electronic Resource
    High Serotonin and 5-Hydroxyindoleacetic Acid Levels in Limbic Brain Regions in a Rat Model of Depression; Normalization by Chronic Antidepressant Treatment (1997)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 69 (1997), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Although alterations in serotonin levels and neurotransmission are associated with depressive disorders and effective antidepressant therapy, the exact cause of these disorders and the mode of action of anti-depressant drugs are poorly understood. In a genetic rat model of depression [Flinders sensitive line (FSL) rats], deviations from normal serotonin (5-HT) levels and metabolism in specific brain regions were determined. The levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in tissue punches of various brain regions were quantitated simultaneously with an HPLC apparatus coupled to an electrochemical detector. In the nucleus accumbens, prefrontal cortex, hippocampus, and hypothalamus of FSL rats, the levels of 5-HT and 5-HIAA were three- to eightfold higher than in control Sprague-Dawley rats. Significant differences in the levels of 5-HT and 5-HIAA in the striatum and raphe nucleus of the “depressed” and normal rats were not observed. After chronic treatment with the antidepressant desipramine (5 mg/kg/day for 18 days), the immobility score in a swim test, as a measure of a behavioral deficit, and 5-HT levels of the FSL rats became normalized, but these parameters in the control rats did not change. The [5-HIAA]/[5-HT] ratio was lower in the nucleus accumbens and hypothalamus of the FSL than in the control rats, and increased after desipramine treatment only in the nucleus accumbens of the FSL rats. These results indicate that the behavioral deficits expressed in the FSL model for depression correlate with increased 5-HT levels in specific limbic sites and suggest the FSL rats as a novel model for clarification of the molecular mechanism of clinically used antidepressant drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1997.69062477.x
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of cholinolytic agents on behavior following development of tolerance to low cholinesterase activity (1971)
    Springer
    Psychopharmacology 20 (1971), S. 32-41 
    Details
    ISSN: 1432-2072
    Keywords: Cholinergic System ; Cholinesterase Activity ; Tolerance ; Operant Response ; Atropine ; Methylatropine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The development of tolerance during periods of chronically low levels of cholinesterase (ChE) induced by administration of diisopropyl fluorophosphate (DFP) is evidenced in systematic changes in behavioral variables. The present experiment was designed to study the biochemical mechanism(s) involved by challenging tolerant and control subjects with pharmacological agents known to affect the cholinergic system: the cholinolytics, atropine and methylatropine. Measures of the free operant behavior showed tolerance to have developed by the 9th injection of DFP, after which the challenge series began. Clear differences were apparent between the effects of the cholinolytic agents on the tolerant and control groups. Dose-response curves for both groups showed similar trends of decreasing performance with increasing dose level until a critical point was reached. With further increases in dose, there was a complete absence of responding in the majority of tolerant subjects, while control animals continued to perform at about 40 per cent normal. The fact that effects of the methylatropine challenge were not significantly different in tolerant and control subjects implies that the biochemical process(es) of tolerance had a major central component.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404056
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  • 3
    Electronic Resource
    Electronic Resource
    Sensitivity of morphine-tolerant rats to muscarinic and dopaminergic agonists: Relation to tolerance or withdrawal (1979)
    Springer
    Psychopharmacology 65 (1979), S. 27-34 
    Details
    ISSN: 1432-2072
    Keywords: Morphine tolerance and withdrawal ; Super- and Sub-sensitivity ; Dopaminergic and cholinergic receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male hooded Wistar rats were treated chronically once daily with morphine sulfate (20 mg/kg SC) after completing a session in an operant chamber. Periodical challenges with morphine (8 mg/kg) prior to the operant session established that tolerance development was virtually complete within 10 days. The morphine-treated rats were more sensitive to the behavioral suppressing effects of apomorphine, a dopamine agonist, and pilocarpine, an acetylcholine agonist, when administered in the tolerant state (morphine given 30 min prior to operant session), regardless of whether they were administered peripherally or directly into the striatum. Conversely, the morphine-treated rats were less sensitive to both agonists when administered in the withdrawal state (morphine given 24 h prior to the operant session). In animals undergoing a similar regimen of chronic morphine treatment, receptor binding studies revealed a lowered affinity (Higher K D apparent) for the dopamine receptor in the striatum of morphine-withdrawn rats, using 3H-spiroperidol as the ligand. The morphine-withdrawn rats also appeared to have fewer muscarinic cholinergic receptors (lower B max), using 3H-QNB as the ligand. The also had a lower concentration of membrane-bound phosphodiesterase modulator protein. In general, no significant differences were observed for the above parameters in the morphine-tolerant rats. These behavioral and neurochemical studies are consistent with the view that morphine-tolerant rats are supersensitive to dopamine and acetylcholine agonists and morphine-withdrawn rats are subsensitive.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00491974
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  • 4
    Electronic Resource
    Electronic Resource
    Behavioural tolerance to arecoline in rats: Cross-tolerance to oxotremorine and prevention by pretreatment with atropine (1986)
    Springer
    Psychopharmacology 89 (1986), S. 118-120 
    Details
    ISSN: 1432-2072
    Keywords: Arecoline ; Tolerance ; Operant responding ; Oxotremorine ; Cross-tolerance ; Atropine pretreatment ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In two experiments tolerance development to the effects of arecoline on operant responding for a water reward was shown to be dose-dependent, complete tolerance developing to a daily dose of 4 mg/kg, but only partial tolerance developing to a daily dose of 8 mg/kg. However, rats chronically treated with the higher dose of arecoline were least affected by a challenge dose of oxotremorine (0.2 mg/kg); i.e. the high dose group exhibited the greatest cross-tolerance to oxotremorine. Moreover, atropine (4 mg/kg) pretreatment prior to arecoline (4 mg/kg) prevented cross-tolerance to oxotremorine, indicating that dispositional mechanisms are unlikely to be involved in tolerance to arecoline.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175202
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  • 5
    Electronic Resource
    Electronic Resource
    Tolerance to low acetylcholinesterase levels: Modification of behavior without acute behavioral change (1972)
    Springer
    Psychopharmacology 26 (1972), S. 127-139 
    Details
    ISSN: 1432-2072
    Keywords: Cholinesterase Activity ; Tolerance ; Drinking ; Scopolamine ; Methyl Scopolamine ; Alpha Methyl-p-Tyrosine ; Diisopropyl Fluorophosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of chronic daily injections of diisopropylfluorophosphate (DFP) and of subsequent acute challenges with scopolamine, methyl scopolamine, and alpha methyl-p-tyrosine (α-mpt) on the drinking behavior of albino rats have been observed. No measurable changes in behavior were noted with the lowest dose of DFP (0.2 mg/kg), while the highest dose (1.0 mg/kg) was found to exceed the LD 50 (0.56 mg/kg/day) for the present regimen of administration. Animals receiving the intermediate doses of DFP (0.4, 0.5 mg/kg) were affected after a latency of approximately 6 days, but their drinking behavior returned to normal during the chronic treatment period, i.e., tolerance developed. Results of subsequent acute challenges with scopolamine indicated that the neurochemical processes underlying the behavior of all DFP-treated subjects were similar, regardless of whether or not the treatment resulted in initial behavioral deficits, and that these processes were different from those underlying the behavior of normal control subjects. Challenges with methyl scopolamine produced effects on the drinking behavior which did not differ for control and DFP-treated animals, while challenges with α-mpt were without significant effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00422099
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  • 6
    Electronic Resource
    Electronic Resource
    Alterations in the effects of dopamine agonists and antagonists on general activity in rats following chronic morphine treatment (1976)
    Springer
    Psychopharmacology 49 (1976), S. 125-130 
    Details
    ISSN: 1432-2072
    Keywords: Morphine tolerance ; Dopamine agonists and antagonists ; General activity ; Supersensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Results of two experiments revealed that morphine produced both time-and dose-dependent effects on the general activity of rats following a single acute administration, depression being observed 30 min after the injection and hyperactivity at 150 min. Tolerance to the depressive effects of morphine was observed within 7 days of chronic, once daily treatments, the depression being replaced by a hyperactivity that included a high degree of self-directed oral stereotyped behaviour. Dose-response analyses of the effects of d-amphetamine, an indirectly acting dopamine agonist, and apomorphine, a directly acting dopamine agonist, revealed a shift in the dose-response curves following chronic morphine treatment, indicating that the animals were supersensitive to these agents. Conversely, the dose-response curve for pimozide, a directly acting dopamine antagonist, was shifted in a direction indicating that the animals were subsensitive to this agent. The dose-response curve for haloperidol, another dopamine antagonist, was unchanged. These findings are consistent with the hypothesis that an increase in the number of dopamine receptors may develop during chronic treatment with morphine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427280
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  • 7
    Electronic Resource
    Electronic Resource
    Acquisition of behaviourally augmented tolerance to ethanol and its relationship to muscarinic receptors (1984)
    Springer
    Psychopharmacology 83 (1984), S. 88-92 
    Details
    ISSN: 1432-2072
    Keywords: Ethanol ; Behaviourally augmented tolerance ; Physiological tolerance ; Muscarinic receptor ; Operant conditioning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two groups of adult male rats were injected daily with ethanol (1.5 g/kg IP in 15% w/v solution) either before (the behaviourally augmented tolerant group) or after (the physiologically tolerant group) being placed in operant chambers. The control groups received daily isotonic saline injections either before or after the operant task. When challenged with ethanol (2.5 g/kg) on day 30 prior to the operant task, the control group was most impaired, while the behaviourally augmented tolerant group was significantly less impaired than the physiologically tolerant group. The two ethanol-treated groups were impaired to the same extent when challenged on day 60. Partial generalization of this behavioural tolerance to ethanol was observed, as the behaviourally augmented tolerant group was less impaired than the physiologically tolerant group for a tail flick response to painful stimuli after an ethanol challenge on day 30. However, the two ethanol-treated groups exhibited similar impairments of locomotor activity after an ethanol challenge on day 40. No differences in muscarinic receptor binding among the control and two ethanol-treated groups were found. These findings demonstrate that behaviourally augmented tolerance to ethanol may be partially generalizable but is unrelated to changes in muscarinic cholinergic receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427429
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  • 8
    Electronic Resource
    Electronic Resource
    Development and disappearance of subsensitivity to pilocarpine following a single administration of the irreversible anticholinesterase agent, DFP (1977)
    Springer
    Psychopharmacology 52 (1977), S. 263-269 
    Details
    ISSN: 1432-2072
    Keywords: DFP ; Anticholinesterase ; Water intake ; Pilocarpine ; Subsensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examined the possibility that subsensitivity to pilocarpine might occur following a single injection of the irreversible anticholinesterase agent, DFP. In one experiment male Sprague-Dawley rats were trained to drink from experimental drinking chambers for 1/2 h per day. After establishment of baselines, pilocarpine hydrochloride (8 mg/kg) was injected i.p. 5 min before the drinking session. One week later DFP or the arachis oil vehicle (1 mg/kg) was injected intramuscularly and injections of pilocarpine were given at varying times thereafter. The suppression of water intake by this dose of pilocarpine was unaffected by pretreatment with arachis oil, but was markedly attenuated by pretreatment with DFP. This subsensitivity was first observed on the second day but had largely disappeared by the 14th day. DFP was found to have comparable effects on water intake and brain acetylcholinesterase activity when the injections were separated by 20 days. In a second experiment the hypothermic effects of pilocarpine were found to be reduced in rats acutely treated with DFP. These data establish that subsensitivity to pilocarpine occurs following a single administration of DFP. This subsensitivity could reflect a reduced sensitivity of postsynaptic receptors to acetylcholine, which may partially account for the behavioural recovery of the rats while acetylcholinesterase activity is still markedly depressed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00426710
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  • 9
    Electronic Resource
    Electronic Resource
    Brain muscarinic cholinergic receptor binding in Roman high- and low-avoidance rats (1981)
    Springer
    Psychopharmacology 72 (1981), S. 143-145 
    Details
    ISSN: 1432-2072
    Keywords: Roman high- and low-avoidance rats ; 3H-QNB binding ; Muscarinic cholinergic receptors ; Psychogenetic differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This experiment sought to determine whether the behavioral differences between the Roman high-(RHA/Verh) and low-avoidance (RLA/Verh) lines of rats could be related to differences in the number and/or affinity of brain muscarinic cholinergic receptors. The binding of the specific muscarinic antagonist 3H-quinuclidinyl benzilate to crude membrane preparations from the cerebral cortex, hippocampus and striatum was determined. There were no significant differences between the two rat lines for the number of muscarinic binding sites (B max) or the apparent dissociation constant (K D) as determined by Scatchard analysis of the saturation isotherms. These data indicate that the behavioral differences between RHA/Verh and RLA/Verh rats cannot be accounted for by differences in the number or affinity of brain muscarinic cholinergic receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431647
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  • 10
    Electronic Resource
    Electronic Resource
    Effects of scopolamine, pilocarpine, and oxotremorine on the exploratory behavior of two psychogenetically selected lines of rats in a complex maze (1981)
    Springer
    Psychopharmacology 72 (1981), S. 135-142 
    Details
    ISSN: 1432-2072
    Keywords: Scopolamine ; Pilocarpine ; Oxotremorine ; Complex maze ; Maze patrolling ; Exploration ; Activity ; Roman High- and Low ; Avoidance rats ; Psychogenetic lines of rats ; Muscarinic cholinergic actions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats of two psychogenetically selected lines received pretest IP injections of scopolamine hydrobromide (0.25, 1.0, or 4.0 mg/kg), pilocarpine hydrochloride (3.0, 6.0, or 12.0 mg/kg) or oxotremorine sesquifumarate (0.2, 0.4, or 0.8 mg/kg) and were subseqently placed in a complex enclosed maze of the Dashiell type that included a small, central, illuminated arena. Animals receiving pilocarpine or oxotremorine injections were pretreated with methscopolamine to counter the peripheral actions of these muscarinic cholinergic agonists. Following vehicle injections, Roman High-Avoidance rats (RHA/Verh) were significantly more active, explored more maze sectors, and required less time to activate the initial 24 different photocell units uniformly distributed throughout the maze than Roman Low-Avoidance rats (RLA/Verh). Scopolamine, pilocarpine, and oxotremorine depressed locomotor activity, reduced the explored area, and increased the time required to activate the initial 24 different photocell units within this complex maze for both RHA/Verh and RLA/Verh rats. Although the doses of scopolamine injected were approximately equally effective in both rat lines (except for total maze activity), the RHA/Verh rats exhibited significant alterations in several measures of maze patrolling after treatment with the lowest dose of pilocarpine, whereas the RLA/Verh rats did not. In contrast, most of the RLA/Verh rats exhibited very pronounced tremors following treatment with the highest dose of oxotremorine, but none of the RHA/Verh rats did. These results demonstrate that manipulation of the central cholinergic system with scopolamine, pilocarpine, or oxotremorine, despite their different pharmacological mechanisms, impair maze patrolling. Furthermore, the results suggest that the two psychogenetically bred lines of rats investigated are differentially sensitive to central cholinergic manipulation with the muscarinic receptor agonists pilocarpine and oxotremorine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431646
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