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Dopamine receptor agonists alter gap prestimulus modulation.

Abstract

An innocuous sensory event (a prestimulus) that briefly precedes a startle-eliciting stimulus (SES) will reduce the amplitude of the subsequently elicited reflex. In three experiments brief silent periods in otherwise continuous noise (gaps) were used as prestimuli to investigate the effects of the D1 dopamine receptor agonist (+/-)-SKF-38393 (SKF) and the dopamine D2 receptor group agonist (-)-quinpirole hydrochloride on gap inhibition of the rat's acoustic startle reflex. Gap durations of 4 and 50 ms were analyzed. Quinpirole (0-1.6 mg/kg) had a biphasic effect on gap inhibition. Lower doses increased gap inhibition, an effect that peaked at the 0.4 mg/kg dose. For higher doses, inhibition returned to control levels for the 4-ms long gap, but remained elevated for the 50-ms long gap. SKF had no effect on gap inhibition, and haloperidol (0.2 mg/kg) reversed the quinpirole-induced increase of gap inhibition. These data implicate the D2 dopamine receptor group in gap inhibition of startle modulation. The results are discussed in terms of the effects of catecholamine agonists on attention.

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BibTeXRIS

D S Leitner, E M Girten. 1997. Dopamine receptor agonists alter gap prestimulus modulation.. https://doi.org/10.1007/s002130050444

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Dopaminergic and adrenergic toxicities on SK-N-MC human neuroblastoma cells are mediated through G protein signaling and oxidative stress.

Dopamine and norepinephrine are neurotransmitters which participate in various regulatory functions of the human brain. These functions are lost in neurodegenerative diseases including Parkinson's disease and Alzheimer's disease. In this study, we used SK-N-MC neuroblastoma cells to investigate the cytotoxicities of high concentrations of dopamine and norepinephrine on neuronal cells. Dopamine, norepinephrine, as well as their corresponding synthetic agonists (SKF38393 and isoproterenol, respectively) triggered SK-N-MC cell death when applied at 50-100 muM persistently for 2 days. This catecholamine-induced cell death appears to be neuronal specific, as demonstrated by their inabilities of triggering apoptosis of A549 lung carcinoma cells and Cos-7 kidney fibroblasts. By pretreating SK-N-MC cells with target-specific inhibitors before administration of catecholamine, components of G protein signaling (i.e. G( s )/cAMP/PKA), monoamine oxidases, nitric oxide synthase, c-Jun N-terminal kinase and oxidative stress were found to be involved in this dopamine/norepinephrine-induced cytotoxicity, which subsequently led to caspase-dependent and -independent apoptotic responses as well as DNA degradation. In contrast, agonists of G( i )-coupled dopamine receptors and adrenergic receptors (quinpirole and UK14,304, respectively) were incapable of triggering apoptosis of SK-N-MC cells. Our results suggest that both G protein (G( s ))-mediated signaling cascade and oxidative stress participate in the dopamine/norepinephrine-induced neuronal apoptosis.

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