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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The present investigation examined the effects of neonatal and adult 6-hydroxydopamine (6-OHDA)-induced lesions of dopaminergic neurons on opioid and tachykinin peptides and their gene expression in the rat basal ganglia. This work was undertaken to determine if changes in these neuropeptide systems were contributing to the differing behavioral responses observed between neonatally and adult-lesioned rats after dopamine agonist administration. [Met5]Enkephalin (ME) content was increased in striatal tissue from both 6-OHDA-lesioned groups when compared with unlesioned controls. Dynorphin-A (1–8) content was not altered by the 6-OHDA lesions. The tachykinin peptides substance P and neurokinin A were significantly decreased in level in the striatum and substantia nigra of neonatally lesioned rats, but not in the adult-lesioned rats, when compared with unlesioned controls. Proenkephalin mRNA abundance (quantified by an RNA-cDNA hybridization technique) and precursor level (as reflected by cryptic ME content) were increased in the striatum of both neonatally and adult-lesioned rats. The abundance of preprotachykinin mRNA coding for the tachykinin peptides was markedly decreased in the neonatally lesioned rats, whereas only a small reduction was observed in the adult-lesioned rats. These results suggest that destruction of dopamine-containing terminals with 6-OHDA elevates the level of ME by accelerating transcriptional and/or translational processes; conversely, the reduced content of tachykinins in neonatally lesioned rats may be due to a reduction in such processes. Thus, preproenkephalin-A and preprotachykinin gene expression are differentially regulated after lesioning of catecholamine-containing neurons, an observation suggesting a close functional relationship among these neurotransmitter systems. Furthermore, of the peptides studied, only levels of the tachykinin peptides were differentially altered in the striatum and substantia nigra of the neonatally lesioned rats compared with adult-lesioned rats; therefore, these peptides may be associated with the distinctive behavioral differences between neonatally and adult 6-OHDA-lesioned rats given dopamine agonists.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 15 (2002), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The ventral pallidum (VP) is situated at the convergence of midbrain dopamine and accumbal opioid efferent projections. Using in vivo electrophysiological procedures in chloral hydrate-anaesthetized rats, we examined whether discrete application of µ- [D-Ala2,N-Me-Phe4,Gly-ol5 (DAMGO)] or κ− (U50488) opioid receptor agonists could alter VP responses to electrical stimulation of ventral tegmental area. Rate suppressions occurred frequently following ventral tegmental area stimulation. Consistent with an involvement of dopamine in this effect, none of the 12 spontaneously active ventral pallidal neurons recorded in rats that had monoamines depleted by reserpine responded to electrical stimulation of ventral tegmental area. Moreover, in intact rats, the dopamine antagonist flupenthixol attenuated evoked suppression in 100% of the neurons tested; however, the GABAA antagonist bicuculline was able to slightly attenuate the response in 50% of the neurons tested. These observations concur with our previous studies in indicating that ventral tegmental area stimulation releases dopamine (and sometimes GABA) onto ventral pallidal neurons. Both DAMGO and U50488 decreased the inhibitory effects of ventral tegmental area stimulation. These effects on the endogenously released transmitter differed from those seen with exogenously applied dopamine, for DAMGO did not alter the efficacy or potency of microiontophoretically applied dopamine. Taken together, these observations suggest that the interaction between DAMGO and dopamine does not occur at a site that is immediately postsynaptic to the dopaminergic input within the VP, but rather that opioid modulation involves mechanisms governing presynaptically released dopamine. These modulatory processes would enable ventral pallidal opioids to gate the influence of ventral tegmental area dopamine transmission on limbic system outputs at the level of the VP.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 9 (1997), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Microiontophoresis was used to investigate the influence of dopamine on GABA- and glutamate-induced responses from ventral pallidal neurons recorded extracellularly in chloral hydrate-anaesthetized rats. Modulation was determined by comparing dopamine-induced alterations in amino acid-induced activity (‘signal’) with dopamine-induced effects on spontaneous firing (‘noise’). A dopamine ejection current-response curve was generated to determine the current levels that did not alter spontaneous firing (‘subthreshold’) and those that produced ∼50% of the maximal dopamine-induced response (ECur50). Co-iontophoresis of dopamine with GABA generally diminished the inhibitory influence of GABA on pallidal neuron firing; 70% of neurons tested with ECur50 dopamine demonstrated a decrease in the signal-to-noise ratio whereas 10% displayed an increase. At subthreshold dopamine ejection currents, 59% of neurons responded with a decrease and 18% responded with an increase in the GABA signal-to-noise ratio. When ECur50 dopamine was co-iontophoresed with glutamate, 84% of the neurons displayed a decrease in the signal-to-noise ratio for glutamate-evoked excitations whereas 11% demonstrated an increase. Subthreshold dopamine ejection currents decreased the signal-to-noise ratio in 62% of the ventral pallidal neurons excited by glutamate and increased the ratio in 23%. These data illustrate that dopamine substantially alters GABA- and glutamate-evoked responses even at ejection currents that are below those necessary to change spontaneous firing. Thus, it appears that neuromodulation is an important means by which dopamine influences ventral pallidal neuronal activity.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Working/episodic memory ; Radial arm maze ; Non-match-to-sample task ; Dopamine ; Apomorphine ; Quinpirole ; SKF38393 ; Sulpiride ; SCH23390 ; Benzodiazepine ; Chlordiazepoxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Central dopaminergic transmission has been implicated in memory processes. The present experiments examined the effects of several direct acting dopaminergic agents on performance of a delayed-non-match-to-sample radial arm maze task. Preadministration of apomorphine (D1-D2 agonist; 0.25, 0.5, and 1.0 mg/kg), quinpirole (D2 agonist; 0.1 mg/kg), or SKF38393 (D1 agonist; 3 mg/kg) increased the latency of choices but did not affect any index of accuracy with a 1 h retention interval. Post-training administration of quinpirole (0.1, 0.2, 1.0, and 2.0 mg/kg), SKF38393 (0.3, 3.0, and 6.0 mg/kg), sulpiride (D2 antagonist; 3, 10, and 30 mg/kg), or SCH23390 (D1 antagonist; 0.01, 0.1, and 1.0 mg/kg) also did not affect accuracy, although quinpirole produced a dose-dependent increase in the latency of choices, assessed 10 h post-treatment. For comparison, pretraining and post-training administration of the benzodiazepine chlordiazepoxide (1, 3, 5 mg/kg) was also tested and produced dose-dependent impairments in mnemonic performance at either a 1 or 4 h retention interval. The effects of chlordiazepoxide are consistent with evidence indicating that GABAergic agents can influence memory processes. In contrast, the present findings indicate that (peripheral administration of dopaminergic agents IS) not sufficient to alter the mnemonic processes required for accurate performance of this DNMTS-RAM task.
    Type of Medium: Electronic Resource
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