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  • 2000-2004  (1)
  • 1985-1989  (1)
  • A69024  (1)
  • Afferent synapses  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Synaptic input and local output of dopaminergic neurons in grafts that functionally reinnervate the host neostriatum (1987)
    Springer
    Experimental brain research 68 (1987), S. 131-146 
    Details
    ISSN: 1432-1106
    Keywords: Ventral mesencephalic grafts ; Electron microscopy ; Afferent synapses ; Tyrosine hydroxylase immunocytochemistry ; Dopaminergic neurons ; Dopaminergic boutons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In adult rats with a unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine pathway, grafts of embryonic ventral mesencephalon can establish extensive efferent connections with the previously denervated host neostriatum and can compensate for motor and sensorimotor asymmetries induced by the lesion. The object of this study was to examine the afferent synaptic inputs to grafted dopaminergic neurons, implanted into a cortical cavity overlying the previously denervated caudate-putamen, using electron microscopic immunocytochemistry. The dopaminergic neurons of the grafts in the same animals had previously been shown to re-innervate the host neostriatum, to form synaptic connections therein and to attenuate the lesion-induced motor asymmetry that occured in response to amphetamine (Freund et al. 1985). In the light microscope, the grafts were found to contain numerous tyrosine hydroxylase-immunoreactive perikarya, dendrites, axons and axonal swellings which had distinct distributions. In addition axons and axonal swellings that were immunoreactive for either substance P or glutamate decarboxylase were present. Electron microscopic analysis of the boutons contacting tyrosine hydroxylase-immunoreactive neurons in the grafts revealed the presence of at least five distinct types of afferent synaptic boutons based on their immunochemistry, morphology, or types of membrane specialization. One type was itself immunoreactive for tyrosine hydroxylase; such synapses are extremely rare in the intact substantia nigra, none were found in the contralateral substantia nigrae or the substantia nigra of a control rat. Three of the remaining types had ultrastructural features that were similar to synaptic terminals that were immunoreactive for substance P or glutamate decarboxylase. These synapses were similar to the types of synapses found contacting dopaminergic neurons in the substantia nigra contralateral to the graft or the substantia nigra of a control rat. The results demonstrate that, in the absence of the normal extrinsic afferent inputs, the intracortical mesencephalic grafts have a well-developed local synaptic circuitry. It is suggested that local circuit regulation of dopaminergic neurons within the graft may, at least in part, be responsible for the maintenance of a normal or close to normal functional activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00255240
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Differential effects of dopamine receptor subtype blockade on performance of rats in a reaction-time paradigm (2000)
    Springer
    Psychopharmacology 148 (2000), S. 355-360 
    Details
    ISSN: 1432-2072
    Keywords: Key words Reaction time ; Motor impairment ; Eticlopride ; Nafadotride ; A69024 ; D1 receptor ; D2 receptor ; D3 receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Pharmacological manipulation of the dopaminergic system with antipsychotic agents disrupts motor behavior. Although most antipsychotic drugs have high affinity for D2 receptors, they also interact with other dopamine receptor subtypes. Therefore, the role of each of these receptor subtypes on motor performance is unclear. Objective: The present study sought to investigate the relative importance of D1, D2, and D3 receptors on performance in a conditioned reaction-time task known to be extremely sensitive to dysfunction of the dopaminergic nigrostriatal pathway. Methods: Rats were trained to release a lever in response to a visual cue within a reaction-time limit to receive a reinforcer (45-mg food pellet). After the behavior of the rats had stabilized, the effects of a D1 (A69024), D2 (eticlopride), and D3 (nafadotride) receptor antagonists were assessed. Results: A-69024 had no effect on performance at any dose tested (0.3, 0.6, and 1.3 mg/kg s.c.). Nafadotride (0.1, 0.3, and 1 mg/kg s.c.) produced only a mild deficit in performance at the highest dose. This deficit was characterized by an increase in the number of delayed responses with a non-significant decrease in the number of premature responses indicative of non-specific sedative effects. In contrast, the D2 receptor antagonist eticlopride (0.005, 0.01, and 0.02 mg/kg s.c.) produced profound deficits in performance as evidenced by a dose-dependent decrease in the number of correct responses. This decrease was accompanied by an increase in the number of delayed responses and a lengthening of the reaction time at the highest doses. Conclusions: These results provide further evidence that the execution of the reaction-time task is dependent preferentially upon the activation of D2 receptors, but not D1 or D3 receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050063
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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