Dynorphinergic GABA neurons are a target of both typical and atypical antipsychotic drugs in the nucleus accumbens shell, central amygdaloid nucleus and thalamic central medial nucleus.
Administration of typical and atypical antipsychotic drugs leads to activation of cells in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus, implicating important shared effects of these drugs. However, the exact cell types responding to antipsychotic drugs in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus are unclear. We report here that, in a rat model, the results of studies using double immunofluorescence labeling with antibodies directed against markers specific to candidate cell types suggest that the cells responding to haloperidol and clozapine in all three sites are: 1) neurons, rather than astrocytes; 2) inhibitory GABA neurons, but not acetylcholinergic neurons; and 3) dynorphin-containing GABA neurons, but not M-enkephalin-containing GABA neurons. The present study provides pharmacological evidence, at the cellular level in vivo, that the shared effects of antipsychotic drugs, whether typical and atypical, is activation of dynorphinergic GABA neurons in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus. Alternative ways to modulate dynorphinergic GABA neuronal activity or its target receptors might present an important new avenue for the treatment of schizophrenia and other psychotic disorders.
Molecular Pharmacology Laboratory, Mailman Research Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA.
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J
Ma
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Ye
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Lange
B M
BM
Cohen
D000109:Acetylcholine / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology; D004399:Dynorphins / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006220:Haloperidol / Q000494:pharmacology; D020646:Intralaminar Thalamic Nuclei / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014150:Antipsychotic Agents; D016760:Proto-Oncogene Proteins c-fos; D005680:gamma-Aminobutyric Acid; D004744:Enkephalin, Methionine; D004399:Dynorphins; D003024:Clozapine; D006220:Haloperidol; D000109:Acetylcholine