Altered Dopamine Release and Uptake Kinetics in Mice Lacking D2 Receptors

摘要: Dysregulation of dopamine transmission is thought to contribute schizophrenic psychosis and drug dependence. Dopamine release regulated by D2 autoreceptors, receptor ligands are used treat addiction. To elucidate the long-term effects autoreceptor activity on signaling, overflow evoked single or paired-pulse stimulation was compared in striatal slices from D2-null mutant wild-type mice. Quinpirole, a D2/D3 agonist, had no effect mice, indicating that receptors only releaseregulating at axon terminal. inhibition GABAB activation unchanged suggesting other G-protein-coupled pathways remained normal absence autoreceptors. Paired-pulse revealed autoinhibition maximal 500 msec after lasted 5 sec. In mutants, response stimuli severely decreased. Experiments with uptake inhibitor nomifensine indicated this caused enhanced rather than reduced release. Analysis kinetics using simulation model suggested an increase velocity uptake, Vmax. These results mice support suggestion autoreceptors transporters interact regulate amplitude timing signals.