Different antipsychotics elicit different effects on magnocellular oxytocinergic and vasopressinergic neurons as revealed by Fos immunohistochemistry

Abstract

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.

Neuroanatomical substrates of the disruptive effect of olanzapine on rat maternal behavior as revealed by c-Fos immunoreactivity

“…Our c-Fos findings are consistent with many previous studies using the immunohistochemistry and in situ hybridization techniques which show that olanzapine induces an increase in c-Fos protein and c-fos mRNA expression in various limbic and striatal regions, including mPFC, NAs, NAc, DLSt, LSv, CeA, the hypothalamic paraventricular nucleus and locus coeruleus (Kiss et al, 2010, Ohashi et al, 2000, Oka et al, 2004, Robertson and Fibiger, 1996, Sebens et al, 1998, Seillier et al, 2003, Verma et al, 2006). These brain regions have been suggested to mediate olanzapine’s antipsychotic action and its clinical effects.…”

Neuroleptics Affect Neuropeptide S and NPSR mRNA Levels in the Rat Brain

“…It is also worth mentioning that there is a substantial diversity in the stimulatory effects of antipsychotics on Fos, Fos/OXY, and Fos/AVP immunostainings with the preferential action of the atypical clozapine over olanzapine and with little effects of risperidone and haloperidol. The data indicating the existence of antipsychotics-induced variabilities in Fos distribution in the PVN, SON, and ACS may be helpful in understanding the extent of their extra-forebrain actions with possible presumption of their functional impact and side effect consequences (Kiss et al 2010). These results are in line with study showing that hypothalamic NPY mRNA level did not change after longterm neuroleptic administration in rats (Rojczyk et al 2015).…”

Endogenous oxytocin levels are associated with the perception of emotion in dynamic body expressions in schizophrenia

“…All participants with SZ were treated with antipsychotics. Drugs that block dopamine receptors may increase plasma oxytocin levels (Kiss et al, 2010), potentially producing group differences in endogenous oxytocin levels that are more driven by medication use than disease. This explanation seems unlikely, however, given that chlorpromazine equivalent dosage was not correlated with plasma oxytocin levels.…”