Brain research
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The effects of chronic 'continuous' infusion and 'intermittent' modes of levodopa/carbidopa administration on apomorphine induced circling behaviour, DA uptake sites (labelled with [3H]mazindol) and D1 and D2 DA receptor binding (labelled with [3H]SCH 23390 and [3H]sulpiride, respectively) were investigated in rats with unilateral 6-OHDA lesions of the medial forebrain bundle. The circling behaviour in response to apomorphine was greatly enhanced following chronic 'intermittent' but not 'continuous' levodopa treatments. Following the 'intermittent' regime, the lower dose of apomorphine induced a period of intense circling with delayed onset and rapid offset, than in rats given either 'continuous' infusion of levodopa or saline. ⋯ This asymmetry in striatal [3H]sulpiride binding was reduced in both groups of rats receiving levodopa. [3H]sulpiride binding in the NAc and OT and [3H]SCH 23390 binding in the striatum, NAc, OT and SNr were unaffected by DA denervation or either regime of levodopa treatments. 'Continuous' infusion and not 'intermittent' injections of levodopa reduced [3H]mazindol binding in the striatal subregions and the frontal cortex on both the denervated and intact sides. The potentiation of the behavioural response to apomorphine by chronic 'intermittent' levodopa treatment does not correspond with the levodopa induced alterations in striatal or extrastriatal DA receptors. In the same group of animals the narrowing of the duration of response to the lower dose of apomorphine may mimic the fluctuations in response to levodopa, seen clinically in long-term levodopa treated parkinsonian patients.
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Intracellular recordings from neurons in the dorsal root ganglion (DRG) and dorsal horn (DH), in an in vitro spinal cord-dorsal root ganglion preparation, were used to investigate the role of tetrodotoxin-resistant (TTX-R) afferent fibers in the sensory synaptic transmission in the superficial DH. Bath application of 25-50 mM potassium to the DRG depolarized the DRG neurons, blocked action potentials in the large neurons, evoked action potentials in slow conducting neurons, and synaptically excited dorsal horn neurons. Excitatory postsynaptic potentials (EPSP) which were evoked in DH neurons by electrical stimulation of large myelinated fibers, but not those evoked by stimulation of small unmyelinated fibers, were blocked by the potassium treatment of the primary afferents. ⋯ Furthermore, high potassium potentiated electrically evoked, TTX-resistant EPSPs in the majority of neurons. This effect was abolished in Na(+)-free solution. These findings indicate that high [K+]e applied to the DRG, dorsal root and peripheral process selectively activates a primary afferent input to the DH, which is sodium-dependent and tetrodotoxin resistant.