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Haloperidol Selectively Remodels Striatal Indirect Pathway Circuits. | LitMetric

Haloperidol Selectively Remodels Striatal Indirect Pathway Circuits.

Neuropsychopharmacology

Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Published: March 2017

Typical antipsychotic drugs are widely thought to alleviate the positive symptoms of schizophrenia by antagonizing dopamine D receptors expressed by striatal spiny projection neurons (SPNs). What is less clear is why antipsychotics have a therapeutic latency of weeks. Using a combination of physiological and anatomical approaches in ex vivo brain slices from transgenic mice, it was found that 2 weeks of haloperidol treatment induced both intrinsic and synaptic adaptations specifically within indirect pathway SPNs (iSPNs). Perphenazine treatment had similar effects. Some of these adaptations were homeostatic, including a drop in intrinsic excitability and pruning of excitatory corticostriatal glutamatergic synapses. However, haloperidol treatment also led to strengthening of a subset of excitatory corticostriatal synapses. This slow remodeling of corticostriatal iSPN circuitry is likely to play a role in mediating the delayed therapeutic action of neuroleptics.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312058PMC
http://dx.doi.org/10.1038/npp.2016.173DOI Listing

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