title: Haloperidol Selectively Remodels Striatal Indirect Pathway Circuits.
abstract: Typical antipsychotic drugs are widely thought to alleviate the positive symptoms of schizophrenia by antagonizing dopamine D2receptors 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.
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors: Luke E
authors: LE
authors: Sebel
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors: Steven M
authors: SM
authors: Graves
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors: C Savio
authors: CS
authors: Chan
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors: D James
authors: DJ
authors: Surmeier
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010546:Perphenazine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D010546:Perphenazine; D006220:Haloperidol