We recently reported that pharmacological manipulations of the dopamine system can produce more than a 4-fold increase in dye coupling between dopaminoceptive neurons in the adult rat striatal complex. During in vivo intracellular recordings, striatal neurons in control rats and in rats that had been treated with 6-hydroxydopamine were injected with either Lucifer yellow or Neurobiotin. Only rats that exhibited severe loss (i.e., larger than approximately 95%) of striatal dopamine terminals displayed a significant increase in the incidence of dye coupling between neurons in adult striatum. Moreover, this increased coupling was present only between neurons of the same morphological cell class, i.e., among clusters of spiny neurons or between aspiny neurons. Combining intracellular labeling of spiny neurons with parvalbumin immunocytochemistry demonstrated that coupling did not occur between anatomically adjacent neurons that comprised immunocytochemically and morphologically distinct cell classes. Therefore, gap junction conductance as reflected by dye coupling appears to undergo upregulation as a consequence of compromises in nigrostriatal and mesolimbic dopamine transmission.