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  • 1
    ISSN: 1432-2072
    Keywords: Social memory ; Cholinomimetic drugs ; Nootropic drugs ; Benzodiazepine inverse agonists ; Psychostimulants ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The recognition of an unfamiliar juvenile rat by an adult rat has been shown to imply short-term memory processes. In this study the effect of various psychotropic drugs on this investigatory behaviour was examined. The procedure was as follows: an unfamiliar juvenile rat was placed in the home cage of an adult rat for 5 min. The time spent by the adult rat in investigating the juvenile was recorded. The adult rat was then immediately treated with vehicle or test compounds, and was again exposed for 5 min to the same juvenile 2 h later. At this time point vehicle-treated rats no longer recognized the juvenile rat, i.e. the time of investigation was similar to that observed during the first presentation. Arecoline (1 and 3 mg/kg IP), physostigmine (0.05 and 0.1 mg/kg SC), RS86 (0.5 mg/IP) and nicotine (0.125 and 0.5 mg/kg IP) reduced in a dose-dependent fashion the time spent in investigating the juvenile during the second exposure. This result cannot be attributed to nonspecific effects, since it was not observed when a different juvenile was used for the second exposure. The effect of arecoline was reversed by scopolamine, but not by methylscopolamine. Aniracetam reduced investigatory behaviour at the dose of 50 mg/kg IP. FG 7142 (5 mg/kg IP) and β-CCM (0.4 mg/kg IP) were also active and their effect was reversed by Ro 15-1788. dl-Amphetamine (0.5 and 1 mg/kg IP), nomifensine (1.25–10 mg/kg IP) and strychnine (0.25 and 0.5 mg/kg IP) were ineffective or reduced this behaviour unspecifically. Social recognition may therefore represent a useful and simple test to detect compounds which enhance short-term, olfactory, memory and to assess in the same animals the specificity of this activity.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Monoamine oxidase type B ; Positron emission tomography ; Ro 19-6327 ; Pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight normal subjects (3 females and 5 males) were studied using intravenous L-11C] deprenyl and positron emission tomography. In a single blind study one subject received tracer alone, one subject received an oral pre-dose of 20 mg of L-deprenyl and 6 subjects received oral pre-doses of 10 to 50 mg of a novel reversible MAO-B inhibitor (Ro 19-6327). Dynamic PET scans beginning 12 h after the oral dose were collected over 90 min and arterial blood was continuously sampled. Data analysis was modelled for two tissue compartments and using an iterative curve fitting technique the value of the rate constant for irreversible binding of L-[11C] deprenyl to MAO-B (k3) in whole brain was obtained for each subject. The dose response curves obtained indicated that a dose of at least 0.48 mg·kg−1 of Ro 19-6327 was necessary for 〉90% decrease in whole brain k3. Inhibition of MAO-B in platelets isolated from blood samples taken at the time of scanning correlated strongly with decrease in whole brain k3 (r=0.949). The results indicate that PET can be used to determine the dose of Ro 19-6327 necessary to inhibit 〉90% of brain MAO-B. This technique is an attractive alternative to traditional large scale patient-based dose-finding studies. Moreover it is shown that inhibition of platelet MAO-B can be used as a marker for central MAO-B inhibition with Ro 19-6327.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 95 (1988), S. 195-199 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Scopolamine cue ; Muscarinic agonists ; Muscarinic antagonists ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus properties of scopolamine, a potent antagonist at muscarinic receptors, were used for testing the discriminative effects of drugs known to act on cholinergic transmission. Rats were trained in a standard two-bar operant conditioning procedure with food as the reinforcer, according to a FR10 schedule. The training dose of scopolamine was progressively reduced from 0.25 mg/kg SC to the low dose of 0.062 mg/kg SC. Scopolarmine yielded an accurate discrimination in all the six rats tested. The generalization gradient resulted in an ED50 of 0.027 mg/kg. The scopolamine cue lasted for 1 h and was of central origin, since it was not mimicked by scopolamine methylbromide. The scopolamine stimulus generalized to atropine and trihexyphenidyl (respective ED50 values 2.20 and 0.21 mg/kg SC). Atropine depressed rate of responding, while trihexyphenidyl did not. Antagonism experiments with both direct agonists at the muscarinic receptor (arecoline and oxotremorine) and indirect agonists, i.e., inhibitors of the acetylcholine esterase [physostigmine and tetrahydroaminoacridine (THA)], led to inconsistent results. Increasing the doses of the agonists in order to block the scopolamine cue may be limited by their rate suppressant effect on responding. Based upon previously published results, it is suggested that the muscarinic agonist cue is more useful than the antagonist cue for investigating muscarinic transmission.
    Type of Medium: Electronic Resource
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