Partial dopamine depletions result in an enhanced sensitivity of residual dopamine neurons to apomorphine.
Extracellular recordings from identified dopamine neurons were used to assess the effect of 6-hydroxydopamine-induced partial lesions of the nigrostriatal dopamine system on the sensitivity of the residual dopamine neurons to the dopamine agonist apomorphine. This was done by testing the response of identified nigral dopamine neurons in control and lesioned rats to systemic apomorphine administration at two time points: 1) 6-10 days post-lesion, when the loss of dopamine cells is nearly complete, and 2) 4-8 weeks post-lesion, which should be sufficient time for changes in dopamine receptor density to occur. As reported previously, dopamine neurons in control rats were inhibited by systemic administration of apomorphine, with their sensitivity being inversely related to their initial firing rate. The sensitivity of the residual dopamine neurons to apomorphine was unaltered in rats tested 6-10 days after depletions of at least 60% of striatal dopamine. However, by 4-8 weeks post-lesion, there was a significant increase in the sensitivity to apomorphine; furthermore, sensitivity was no longer related to baseline firing rate, but instead was uniformly high in all dopamine neurons tested at this time. This enhanced sensitivity was not altered by hemisection of the striatonigral projection, suggesting that the increased sensitivity to apomorphine was most likely a result of a time-dependent up-regulation of somatodendritic autoreceptors on the residual dopamine neurons.
Pucak
M L
ML
Department of Behavioral Neuroscience, University of Pittsburgh, Pennsylvania 15260.
Grace
A A
AA
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000172:deficiency* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004594:Electrophysiology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013378:Substantia Nigra / Q000502:physiology
D001058:Apomorphine; D004298:Dopamine