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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Antipsychotic drugs (APDs) have been primarily characterized for their effects on dopaminergic terminal regions in the brain, especially within the corpus striatum. Efferent GABA pathways are the primary outflow of striatal processing via their projections to the substantia nigra and the globus pallidus (GP). In the current study, we analyzed changes in pallidal GABA function following acute APD administration by means of in vivo microdialysis, followed by immunolabeling of presynaptic GABA terminal density in the contralateral hemisphere of the same animals. Acute administration of the atypical APD, clozapine (10 or 30 mg/kg, s.c.), produced a dose-dependent decrease in extracellular GABA. A corresponding dose-dependent increase in the density of presynaptic terminal GABA immunolabeling in the GP was found. In contrast, the typical APD, haloperidol (1 or 3 mg/kg, s.c.), had no significant effects on either measure, although a non-significant increase in extracellular GABA and decrease in the density of GABA terminal immunolabeling was noted. Paw retraction tests conducted during the time of microdialysis showed that haloperidol produced a typical pattern of highly pronounced motor impairment, while clozapine showed an atypical profile of minimal catalepsy. These complementary results obtained from in vivo neurochemistry and presynaptic neurotransmitter labeling suggest that systemic clozapine suppresses neuronal GABA release within the GP. This decrease in released pallidal GABA may play a role in the low motor side-effect liability of atypical APDs.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 654 (1992), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 605-610 
    ISSN: 1432-1912
    Keywords: Key words: Microdialysis – Dopamine – 3-PPP – Caudate-putamen – Nucleus Accumbens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The ability of the enantiomers of 3-PPP (3-(3-hydroxyphenyl)-N-n-propylpiperidine) to modify the extracellular concentration of dopamine (DA) in the caudate-putamen and the nucleus accumbens of awake rats was assessed using intracranial microdialysis. The enantiomers and the racemate were directly infused at 3 incremental concentrations (1–100 μM) or systemically administered by subcutaneous injection (10 mg/kg). Both systemic administration and direct infusion of (–)3-PPP at the highest concentration (100 μM) significantly increased extracellular DA in both brain regions. This increase was also seen in the presence of higher extracellular DA levels following reuptake inhibition by nomifensine (10 μM). In contrast to the effects of (–)3-PPP, systemic administration of both (+)3-PPP and (±)3-PPP decreased DA levels. Infusion of (±)3-PPP led to slight increases in DA levels in both brain regions at the highest concentration (100 μM), while (+)3-PPP at 100 μM also produced a significant increase in the caudate-putamen, but not in the nucleus accumbens. However, in the presence of nomifensine-induced elevations in extracellular DA, (+)3-PPP produced a significant decrease in DA concentrations in both brain regions. These results support previous findings that the enantiomers of 3-PPP show unique profiles in their in vivo effects on DA terminal functions. Furthermore, these effects are dependent on the mode of 3-PPP administration, the brain region in which DA overflow is measured, and the level of basal extracellular DA.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 605-610 
    ISSN: 1432-1912
    Keywords: Microdialysis ; Dopamine ; 3-PPP ; Caudate-putamen ; Nucleus Accumbens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ability of the enantiomers of 3-PPP (3-(3-hydroxyphenyl)-N-n-propylpiperidine) to modify the extracellular concentration of dopamine (DA) in the caudate-putamen and the nucleus accumbens of awake rats was assessed using intracranial microdialysis. The enantiomers and the racemate were directly infused at 3 incremental concentrations (1–100 μM) or systemically administered by subcutaneous injection (10 mg/kg). Both systemic administration and direct infusion of (−)3-PPP at the highest concentration (100 μM) significantly increased extracellular DA in both brain regions. This increase was also seen in the presence of higher extracellular DA levels following reuptake inhibition by nomifensine (10 μM). In contrast to the effects of (−)3-PPP, systemic administration of both (+)3-PPP and (±)3-PPP decreased DA levels. Infusion of (±)3-PPP led to slight increases in DA levels in both brain regions at the highest concentration (100 μM), while (+)3-PPP at 100 μM also produced a significant increase in the caudate-putamen, but not in the nucleus accumbens. However, in the presence of nomifensine-induced elevations in extracellular DA, (+)3-PPP produced a significant decrease in DA concentrations in both brain regions. These results support previous findings that the enantiomers of 3-PPP show unique profiles in their in vivo effects on DA terminal functions. Furthermore, these effects are dependent on the mode of 3-PPP administration, the brain region in which DA overflow is measured, and the level of basal extracellular DA.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Oral movements ; Chronic neuroleptics ; Tardive dyskinesia ; Fast-fourier ; Haloperidol ; Fluphenazine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Oral movements (OMs) in rats chronically administered haloperidol (HAL), fluphenazine (FLU), or no drug were recorded using a computerized video analysis system which measured the distance between two fluorescent dots painted above and below the rat's mouth. The resulting data was analyzed using fast-fourier analysis. Following an initial period of sedation (decreased energy at all frequencies), the drugged animals (and especially the FLU animals) began to show increased oral movements of 1–2 Hz, an effect which increased substantially upon drug withdrawal. This is precisely the altered energy spectrum observed in humans with tardive dyskinesia.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2072
    Keywords: Tardive dyskinesia ; Animal models ; Depot neuroleptics ; Haloperidol ; Fluphenazine ; D1 vs D2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were chronically administered either haloperidol (HAL) or fluphenazine (FLU) via depot injections for 8 months, given these same drugs in their drinking water for the next 2 months, and then withdrawn from the drugs. Throughout the experiment the animals were tested repeatedly in an enclosed tube using a computerized device which measured computer-scored movelets (CSMs) and, in the latter half of the experiment, were also scored by a human observer in the tube, as well as in an open cage, for observed oral movements (OMs). In the tube, the animals in both neuroleptic-treated groups showed initial decreases in the number of CSMs and made sluggish CSMs; these effects were generally larger in the FLU animals. After 6 months of chronic neuroleptics, the HAL-treated animals showed increased oral movements, both as reported by the human observer and in CSMs of all amplitudes, and this effect increased upon drug withdrawal. FLU-treated animals showed a more persistent depression of both OMs and CSMs of large amplitudes. However, the behavior most characteristic of both neuroleptic-treated groups was the gradual development of increases in CSMs of the smallest amplitudes measurable. A different pattern was observed in the open cage test, where both neuroleptic groups showed significant increases in vacuous OMs during drug administration which rapidly became attenuated upon drug withdrawal. These results indicate a complex syndrome of oral activity in the drugged animals which changed over time. The measure of oral activity which most clearly showed the time-course for late-onset changes in oral activity was CSMs of the smallest amplitudes.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 100 (1990), S. 404-412 
    ISSN: 1432-2072
    Keywords: Neuroleptics ; Haloperidol ; Tardive dyskinesia ; Dystonia ; Animal models ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were administered equivalent doses of haloperidol for either 28 days or 8 months using one of two different drug regimens: intermittent (i.e., weekly injections) or continuously (via drinking water and osmotic minipumps). Oral movements were determined by human observers and by a computerized video analysis system, which determined number and amplitude of jaw openings and closings (computer-scored movelets “CSMs”) as well as the slope (amplitude/duration) and frequency spectrum (fourier transform) of oral activity. The two drug groups developed distinctively different changes over time. Continuous administration resulted in late-onset oral activity changes at 1–3 Hz and withdrawal increases in CSMs, a pattern expected of tardive dyskinesia. Intermittent treatment produced a primed dystonia-like pattern: large amplitude CSMs which had steep onset slopes and a peak energy at 4–7 Hz. These results demonstrate the importance of drug regimen in determining the type of neuroleptic-induced dyskinesias which develop with prolonged neuroleptic treatment in rodents.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 15 (1998), S. 1640-1642 
    ISSN: 1573-904X
    Keywords: haloperidol ; plasma ; ovariectomy ; estrogen ; therapeutic drug monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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