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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 37 (1979), S. 309-316 
    ISSN: 1432-1106
    Keywords: Nigral efferents ; Striatum ; Tectum ; Dorsal tegmental decussation ; Circling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extensive unilateral or bilateral electrolytic ablation of the rat superior colliculus failed to reduce apomorphine- or amphetamine-induced rotation in animals with a unilateral 6-hydroxydopamine lesion of one nigro-striatal dopaminergic pathway. These findings suggest that a nigro-tectal pathway does not play a crucial role in mediating the circling response caused by striatal dopamine receptor stimulation. However, electrolytic lesions of the dorsal tegmental decussation reduced apomorphine- but not amphetamine-induced rotation in such animals, perhaps by sectioning some commissural pathway between the two nigro-striatal systems.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 79 (1983), S. 226-230 
    ISSN: 1432-2072
    Keywords: Neuroleptics ; Perioral responses ; Cholinergic agents ; Tardive dyskinesia ; Acute dystonic reactions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats treated continuously for 4 months with haloperidol (1.4–1.6 mg/kg/day), trifluoperazine (4.5–5.1 mg/kg/day), or sulpiride (102–110 mg/kg/day), but not clozapine (23–26 mg/kg/day), exhibited an increased frequency of chewing jaw movements. Chewing in both control and haloperidol-treated rats was increased by acute administration of the cholinergic agents pilocarpine or physostigmine. Physostigmine or pilocarpine also induced abnormal gaping jaw movements; physostigmine-induced gaping was more prevalent in haloperidol-treated rats than control rats receiving physostigmine alone. Acute administration of the anticholinergic agents scopolamine and atropine decreased chewing in control animals and reduced haloperidol-induced chewing to control values or below. The effects of these cholinergic manipulations suggest that neuroleptic-induced perioral responses in rats do not resemble tardive dyskinesia in man.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Haloperidol ; Sulpiride ; Striatum ; Supersensitivity ; Dopamine receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Administration of haloperidol (1.4–1.6 mg/kg/day) for up to 12 months or sulpiride (102–109 mg/kg/day) for between 6 and 12 months increased the frequency of purposeless chewing jaw movements in rats. N,n-propylnorapomorphine (NPA) (0.25–2.0 mg/kg SC) did not induce hypoactivity in haloperidol-treated rats at any time; sulpiride treatment for 9 and 12 months caused a reduction in the ability of NPA to induce hypoactivity. Haloperidol, but not sulpiride, treatment enduringly inhibited low dose apomorphine effects (0.125 mg/kg SC). After 12 months, sterotypy induced by high doses of apomorphine (0.5–1.0 mg/kg) was exaggerated in haloperidol-, but not sulpiride-treated rats. Bmax for specific striatal 3H-spiperone binding was increased by haloperidol, but not sulpiride, treatment throughout the study. Bmax for 3H-NPA binding was elevated only after 12 months of both haloperidol and sulpiride treatment. Bmax for 3H-piflutixol binding was not alfered by chronic haloperidol or sulpiride treatment. Striatal dopamine-stimulated adenylate cyclase activity was inhibited for the 1st month of haloperidol treatment, thereafter returning to control levels; dopamine stimulation was increased after 12 months of sulpiride treatment. Striatal acetylcholine content was increased after 3 and 12 months of treatment with haloperidol, but was not affected by sulpiride. Chronic administration of sulpiride does not induce identical changes in striatal dopamine function to those caused by haloperidol.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Dopamine ; Acetylcholine ; Acute dystonia ; Peri-oral behaviour ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Continuous administration of haloperidol, sulpiride, or cis-flupenthixol, but not of domperidone or apomorphine, to Wistar rats for up to 3 weeks caused an increase in spontaneous purposeless chewing movements. Treatment with physostigmine and pilocarpine, but not neostigmine, for up to 3 weeks increased chewing, whilst scopolamine decreased chewing. Metergoline and cyproheptadine, but not quipazine, increased chewing after only 1 and 7 days but not thereafter. Chewing was not altered following treatment with compounds acting on GABA or noradrenaline systems or by a range of non-neuroleptic agents inducing dystonia in man. The enhancement of chewing induced by neuroleptic and cholinomimetic drugs was reduced by acute treatment with scopolamine, and reverted to control levels following drug withdrawal. Neuroleptic-induced purposeless chewing in Wistar rats appears to be primarily influenced by cerebral dopamine and acetylcholine function and may resemble acute dystonia, rather than tardive dyskinesia.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1106
    Keywords: 6-OHDA lesion ; Foetal ventral mesencephalic graft ; L-DOPA and carbidopa ; Parkinson's disease ; Circling behaviour ; Neural grafting ; Gliosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In rats with a unilateral 6-OHDA lesion of the nigrostriatal pathway, foetal ventral mesencephalic grafts implanted into the 6-OHDA-lesioned striatum produced a reduction in apomorphine-induced contralateral rotation, and complete abolition of (+)-amphetamine-induced ipsilateral rotation. The graft-induced reduction of apomorphine and (+)-amphetamine-induced rotation was not affected by chronic 27 week administration of L-DOPA and carbidopa to rats receiving foetal grafts. TH-immunohistochemistry revealed 〉96% loss of dopamine cells in the substantia nigra ipsilateral to the 6-OHDA lesion in all animals, but cell loss in the ipsilateral ventral tegmental area was more variable (21–46% of the intact side). TH-positive cells in the intact substantia nigra and ventral tegmental area were not affected by chronic treatment with L-DOPA and carbidopa. In the lesioned striatum of rats receiving sham grafts, no TH-positive cells or fibres were seen. In the 6-OHDA-lesioned striatum of animals receiving foetal grafts, many TH-positive cells were seen in the grafts and chronic treatment with L-DOPA and carbidopa did not reduce cell survival. GFA-P immunohistochemistry revealed that a unilateral 6-OHDA lesion followed by a sham graft was not associated with a reactive gliosis reaction in the striatum at the time of study (38 weeks after lesion surgery and 30 weeks after sham-graft), and treatment of such rats with L-DOPA and carbidopa was also without effect on glia. In contrast there was a marked gliosis in the striatum surrounding foetal grafts which was unaffected by chronic treatment with L-DOPA and carbidopa. The grafts themselves were surrounded by a rim of glial cells, and the glial density within the grafts was higher in animals receiving chronic L-DOPA and carbidopa treatment. However, there was no obvious relationship between the number of TH-positive cells within the grafts, or graft volume, and glial cell density within the grafts. These results suggest that long-term treatment with L-DOPA and carbidopa does not impair either the behavioural recovery produced by foetal ventral mesencephalic grafts in rats or the long-term survival of grafts as revealed by TH-immunohistochemistry. The presence of a foetal graft is associated with a reactive gliosis in the implanted striatum, which was not altered by long-term treatment with L-DOPA and carbidopa. However such treatment did result in an increase in glial density within the grafts themselves.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1106
    Keywords: Circling behaviour ; Angular complex ; GABA ; Substantia nigra ; Striatum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Unilateral injection of muscimol into the angular complex (lateral periaqueductal grey matter and adjacent reticular formation) caused ipsiversive rotation. Focal injection of picrotoxin into the same site produced contraversive rotation. Administration of apomorphine to animals with a unilateral 6OHDA lesion of the left medial forebrain bundle caused contraversive rotation. Focal injection of muscimol into the angular complex reversed the direction of rotation such that apomorphine administration now produced ipsiversive circling. Unilateral injection of muscimol into substantia nigra zona reticulata caused contraversive rotation. Focal injection of picrotoxin into the same site produced ipsiversive rotation. The prior injection of muscimol into the ipsilateral angular complex prevented the contraversive rotation induced by intranigral administration of muscimol such that animals now showed ipsiversive circling. In both 6-OHDA-lesioned animals and animals receiving intranigral muscimol, focal injection of muscimol into the angular complex caused a reversal in the direction of circling through loss of the postural component with no obvious change in locomotor activity. Bilateral electrolytic lesions of the angular complex overall had no effect on amphetamine-induced locomotion. Manipulation of GABA function in the angular complex alters circling behaviour initiated from the striatum or substantia nigra by altering the postural component without affecting the locomotor response of the animals. The data suggest a critical role for the angular complex as an outflow station from basal ganglia.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2072
    Keywords: Chronic neuroleptic ; Dopamine ; Supersensitivity ; Striatum ; Mesolimbic area
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous work has shown that 6–12 months continuous trifluoperazine (TFP) administration to rats causes striatal dopamine receptor supersensitivity. We have now replicated our original findings in the striatum and report concurrent changes in mesolimbic dopamine function during chronic TFP (2.8–4.0 mg/kg/day) administration for 6 months. Initial inhibition of apomorphine-induced stereotyped behaviour, which lasted for 2 weeks after the beginning of drug administration, was replaced by an exaggerated response to apomorphine (0.5 mg/kg SC) after 6 months drug intake. Striatal dopamine sensitive adenylate cyclase activity was inhibited at 1 and 3 months, but by 6 months was enhanced compared to control values. Mesolimbic adenylate cyclase activity was inhibited after 2 weeks and thereafter returned to control levels. Dopamine-identified 3H-spiperone binding sites (Bmax) in the striatum were increased by 2 weeks, reduced at 1 month and increased again at 6 months. In mesolimbic areas Bmax was increased at 2 weeks and 1 month but thereafter returned to control levels. The dissociation constant (k D) of specific 3H-spiperone binding was increased in the striatum and mesolimbic areas at 1 month and 2 weeks respectively. The results show differential changes in dopamine function in striatal and mesolimbic brain areas during 6 months continuous TFP administration to rats.
    Type of Medium: Electronic Resource
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