Amperozide and clozapine but not haloperidol or raclopride increase the secretion of oxytocin in rats

Abstract

The aim of the present study was to investigate whether amperozide, an antipsychotic drug which possesses anti-aggressive and anxiolytic-like properties, stimulates the secretion of oxytocin and if so, by which receptor mechanism. For this purpose, female or male Sprague Dawley rats were given amperozide (0.5, 2.5 and 5.0 mg/kg IP), ritanserin (5.0 mg/kg), raclopride (2.0 mg/kg) and prazosin (1.0 mg/kg) and were subsequently decapitated for collection of blood (30 and 120 min) after injection. Oxytocin levels were measured with radioimmunoassay. Amperozide 2.5 and 5 mg/kg increased plasma levels of oxytocin significantly (P < 0.05 and < 0.001). The effect appeared maximal about 30 min after injection of the drug and oxytocin levels were almost back to basal within 120 min. Similar effects were obtained in female and male rats as well as in animals that were freely fed or food deprived for 24 h. CSF levels of oxytocin were also increased. Ritanserin, a 5-HT2-receptor antagonist but not the D2 receptor antagonist raclopride or the alpha 1-adrenoceptor antagonist prazosin stimulated oxytocin release. In addition, clozapine, a neuroleptic with potent HT2-antagonistic properties, was a potent releaser of oxytocin, whereas haloperidol was without effect. A possible role for oxytocin in the behavioural effects of amperozide and clozapine remains to be explored.

Social Interaction Deficits Caused by Chronic Phencyclidine Administration are Reversed by Oxytocin

“…These findings are consistent with clinical observations that the atypical antipsychotic clozapine normalizes some of the negative symptoms of schizophrenia, while haloperidol fails to show significant effects on these same symptoms (Corrigan et al, 2003). Interestingly, clozapine but not haloperidol, enhances OT release from central nervous system neurons (Uvnas-Moberg et al, 1992). The data presented here would suggest that the potential therapeutic effects of clozapine on the negative symptoms of schizophrenia may, in fact, be mediated by alterations in the central oxytocinergic system and identify the CeA as a potential site for this action.…”

Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

“…74 In addition, treatment with the atypical antipsychotic clozapine normalizes some of the negative symptoms of schizophrenia 75 and can enhance the release of Oxt from neurons of the central nervous system. 26 Consistent with the aforementioned effects, OxtÀ/À mice have significant deficits in some of their cognitive functioning. OxtÀ/À mice have impaired social memory.…”

“…[18][19][20][21][22] In patients diagnosed with either schizophrenia or obsessive compulsive disorder, there have been reports of elevated Oxt baseline concentrations in cerebral spinal fluid (CSF) in some, 23,24 but not all, 25 studies. Rats treated with antipsychotics have elevated Oxt secretion, 26 suggesting that endogenous Oxt may be important for the effects of antipsychotic drugs. Also in rats, pharma-cologically disrupted PPI can be restored with Oxt administration.…”

Negative correlation between cerebrospinal fluid oxytocin levels and negative symptoms of male patients with schizophrenia

“…Since the CSF oxytocin levels were not normally distributed, log transformation was applied prior to statistical analyses to achieve normal distribution. Because previous studies suggest that some antipsychotic and antidepressant medications increase oxytocin secretion (Uvnas-Moberg et al, 1992;Uvnas-Moberg et al, 1999), chlorpromazine and imipramine equivalent doses were examined as possible confounders. Statistical analyses were performed using the Statistical Package for the Social Sciences version 11.0 (SPSS Japan, Tokyo, Japan).…”