The delayed onset of action of antipsychotic drugs (APDs) during the treatment of schizophrenia has been hypothesized to temporally correlate with the induction of depolarization block in rat mesencephalic dopamine (DA) cell groups. Nevertheless, it is unknown whether these drugs also exert a delayed action on the dopaminoceptive postsynaptic target cells in the striatal complex. Using in vivo intracellular recording and dye labeling techniques, the effects of APDs on dye coupling were examined in subregions of the striatal complex defined by double staining for calbindin immunoreactivity. Rats treated repeatedly with APDs were found to exhibit a 66–71% higher incidence of coupling that occurred in a drug- and a region-specific manner, that is, both drug treatments increased dye coupling in the limbic-associated accumbens shell region whereas only haloperidol increased dye coupling in the motor-related striatal matrix and accumbens core regions. In addition, cells located in regions in which dye coupling was altered also showed significantly higher input resistance. These changes were not observed in response to DA receptor blockade by acute drug administration or when haloperidol was administered for a period sufficient to induce DA receptor supersensitivity but not DA cell depolarization block (i.e., 2 weeks). Therefore, alteration in dye coupling appears to be correlated temporally with the induction of DA cell depolarization block. The finding that both APDs exert a common action on neurons in the accumbens shell region is consistent with its identification as the site of therapeutic drug actions, whereas the capacity of haloperidol to also affect cells in the motor-related matrix and core regions correlates with its high propensity to induce extrapyramidal side effects.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.