The neural substrate of brain-stimulation reward : Neurochemical evidence from amicrodialysis study

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The purpose of this research is to elucidate the neurochemical substrates of brain-stimulation reward mechanisms. Dopamine(DA)is known to be one of the neurotransmitters involved in the mediation of intracranial self-stimulation(ICSS)behavior. With the current developments of microdialysis and sensitive detection techniques, it has been possible to understand how the concentrations of the transmitters and their metabolites change at specific synaptic regions in the brain of behaving animals. In the first experiment, we have investigated using this technique whether an increase in extracellular DA release does occur during spontaneous ICSS of normal rats. we observed that ICSS of the medial forebrain bundle(MFB)produced a marked increase in extracellular concentrations of the main DA metabolites 3, 4-dihydroxyphenylacetic acid(DOPAC)and homovanillic acid(HVA)in the nucleus accumbens(NAC). However, in these rats the increase in extracellular DA was small and not significant. Our data wer … More e interpreted as indicating dw ICSS increased the release of DA from the nerve terminals which was quickly taken up into the terminals, thus resulting in no apparent change in the DA concentrations in the dialysate samples under normal conditions. Support for this interpretation is provided by the second experiment in which ICSS of the MFB has been found to cause a pronounced increase in extracellular DA in the NAC which can be demonstrated in the presence of an uptake inhibitor, nomifensine. In the third experiment, we compared the changes in the extracellular levels of DA, DOPAC and HVA from three dopaminergic terminal regions, the medial frontal cortex(MFC), NAC and striatum(STR). ICSS of the MFB in nomifensine-treated rats caused an increase in the extracellular DA level in the MFB and NAC but not in the STR. ICSS also increased the extrasellular concentrations of DOPAC and HVA to a similar extent in the MFC and NAC and to a lesser extent in the STR. The results indicate that ICSS of the MFB preferentially activates the mesocorticolimbic DA systems, thereby increases in the release of DA and its metabolism being produced in their terminal regions, the MFC and NAC. Less