Biomedical subjects

M R Kilpatrick

Publications and source records attributed to M R Kilpatrick.

4 recordsLinked to original sources

PubMed2000

Correlation between behavior and extracellular dopamine levels in rat striatum: comparison of microdialysis and fast-scan cyclic voltammetry.

Recently, fast-scan cyclic voltammetry (FSCV) has been adapted for real-time measurements of evoked dopamine (DA) release and uptake in freely moving rats. Using the advantages of this experimental design in combination with behavioral measures, we examined the effect of GBR 12909 (20 mg/kg, i.p.), a selective DA uptake inhibitor, on striatal extracellular DA dynamics and compared these data to that obtained by microdialysis. These studies established that both techniques report changes in DA that correlate with the kinetics of GBR 12909-induced behavioral effects. However, the time course of changes in evoked DA levels detected by FSCV was more closely linked with the changes in stereotypy than microdialysis measurements.

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PubMed2000

Extracellular dopamine dynamics in rat caudate-putamen during experimenter-delivered and intracranial self-stimulation.

Intracranial self-stimulation is an operant behavior whereby animals are conditioned to press a lever in order to receive an electrical stimulation of their dopamine neurons. This paradigm is thought to stimulate brain reward pathways and, as such, has been used to clarify the role of dopamine in reward. Striatal extracellular dopamine concentrations were monitored during the acquisition and maintenance of self-stimulation and compared to dopamine release generated by experimenter-delivered and yoked stimulation. Fast-scan cyclic voltammetry in conjunction with carbon-fiber microelectrodes was used to monitor evoked dopamine release in the caudate-putamen during electrical stimulation of the substantia nigra/ventral tegmental area. The sub-second temporal resolution of fast-scan cyclic voltammetry coupled with the micron spatial resolution of the microelectrodes allowed for the measurement of dopamine neurotransmission in real-time. Single experimenter-delivered stimulations, identical to those used during self-stimulation, evoked dopamine release in the caudate-putamen both before and after the self-stimulation sessions. Likewise, yoked stimulations of the substantia nigra/ventral tegmental area delivered to animals untrained to perform self-stimulation resulted in an increase in extracellular dopamine levels. During training sessions, experimenter-delivered stimulations evoked dopamine release. However, as the animals began lever-pressing, extracellular dopamine levels subsequently declined. Taken together, these results suggest that dopamine functions as an alerting device, wherein increases in extracellular dopamine are obtained by unpredicted or novel rewarding stimuli, but not by those which can be anticipated.

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PubMed1999

Improving data acquisition for fast-scan cyclic voltammetry.

Described is an improved data acquisition system for fast-scan cyclic voltammetry (FSCV). The system was designed to significantly diminish noise sources that were identified in previously recorded FSCV measurements for the detection of neurotransmitters. Minimized noise is necessary to observe the low concentrations of neurotransmitters that are physiologically important. The system was based on a high-speed, 16-bit AD/DA acquisition board that allowed high scan rates and better resolved the small faradaic currents which remained after background subtraction. Irregularities that occur when independent timing sources are used for generation of the voltage waveform and collection of the current can create large noise artifacts near the voltage limits during FSCV. These were eliminated by the use of a single acquisition board that generated the voltage waveform and collected the current. Noise from frequency drift of the power line was eliminated through the use of a phase-locked loop. To demonstrate the improved performance of the system, data were collected using carbon-fiber microelectrodes in a flow injection analysis system and in brain slices. This new data acquisition system performed significantly better than another system previously used in our laboratory without these features. The improved detection limits of the new system allowed clearly resolved current spikes featuring pre-release "feet" to be recorded adjacent to individual mast cells following chemical stimulation. When combined with false-color plots, the low-noise system facilitated identification of dopamine release in a freely moving animal.

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PubMed1999

Effect of tolcapone, a catechol-O-methyltransferase inhibitor, on striatal dopaminergic transmission during blockade of dopamine uptake.

To examine the mechanisms of tolcapone in the central nervous system (CNS), we analyzed alterations in parameters of striatal dopamine transmission induced by this drug (30 mg/kg) co-administered with the selective dopamine uptake inhibitor, GBR 12909 (10 mg/kg). Using microdialysis in freely moving rats, it was determined that combined administration of tolcapone with GBR 12909 resulted in a further increase of dopamine levels over that obtained without the catechol-O-methyltransferase inhibitor, while tolcapone alone failed to change dopamine levels. Fast-scan cyclic voltammetric monitoring of electrically evoked dopamine did not show any changes in dopamine release after the combination of the drugs, but there was a pronounced decrease in the rate of dopamine clearance after GBR 12909 alone and when co-administered with tolcapone. These data indicate that in rat striatum, a tolcapone-induced increase in extracellular dopamine is not observed because of the presence of uptake. These results also support the hypothesis that under normal conditions, uptake, rather than metabolism, control extracellular levels of dopamine.

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