Different antipsychotics elicit different effects on magnocellular oxytocinergic and vasopressinergic neurons as revealed by Fos immunohistochemistry.
Acute administration of antipsychotics elicits regionally distinct patterns of Fos expression in the rat brain. Stimulation of oxytocin (OXY) and vasopressin (AVP) release in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei indicates that antipsychotics may play a role in autonomic, neuroendocrine, and behavioral processes. This study was focused to reveal the responsiveness of hypothalamic OXY- and AVP- producing magnocellular neurons, in terms of quantitative and topographical distinctions, to antipsychotics displaying different pharmacological profiles. Naive male Wistar rats were injected intraperitoneally with haloperidol (1 mg/kg), clozapine (30 mg/kg), olanzapine (30 mg/kg), risperidone (2mg/kg), and vehicle (5% chremophor) and were sacrificed 60 min later by a fixative. Fos, Fos/OXY, and Fos/AVP labelings were visualized by immunohistochemistry in the SON, 5 accessory (ACS) cell groups, and 4 distinct PVN subdivisions using a computerized light microscope. Most apparent activation of single Fos, Fos/OXY, and Fos/AVP cells was induced by clozapine and olanzapine; effects of risperidone and haloperidol were substantially lower; no colocalizations were revealed in naive or vehicle treated control rats. The data indicate the existence of a substantial diversity in the stimulatory effect of the selected antipsychotics on quantity of Fos, Fos/OXY, and Fos/AVP immunostainings with the preferential action of the atypicals clozapine over olanzapine and little effects of risperidone and haloperidol. Variabilities in Fos distribution in the PVN, SON, and ACS induced by antipsychotics may be helpful to understand more precisely the extent of their extra-forebrain actions with possible presumption of their functional impact and side effect consequences.
Laboratory of Functional Neuromorphology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia. ueenkiss@savba.sk
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Kiss
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Bundzikova
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Pirnik
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JD
Mikkelsen
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D000077152:Olanzapine; D010121:Oxytocin / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism*
D014150:Antipsychotic Agents; D016760:Proto-Oncogene Proteins c-fos; D014667:Vasopressins; D001569:Benzodiazepines; D010121:Oxytocin; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine