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 α1-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.
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Everitt BJ, Meister B, Hökfelt T (1992) The organization of monoaminergic neurons in the hypothalamus in relation to neuroendocrine integration. In: Nemeroff CB (ed) Neuroendocrinology, chapter 6, CRC Press, Boca Raton, pp 87–128
Gustafsson B, Christensson E (1990) Amperozide-a new putatively antipsychotic drug with a limbic mode of action on dopamine mediated behaviour. Pharmacol Toxicol Suppl 1:12–17
Hansen S, Ferreira A (1985) Foodintake, aggression and fear behaviour in the mother rat: control by neural systems concerned with milk ejection and maternal behaviour. Behav Neurosci 100:64–70
Keverne EB, Levy F, Poindron P, Lindsay DR (1983) Vaginal stimulation-an important determinant of maternal bonding in sheep. Science 219:81–83
Numan M (1988) Maternal behavior. In: Knobil E et al (eds) The physiology of reproduction. Raven Press, New York
Pedersen CA, Prange AJ, Jr (1979) Induction of maternal behavior in virgin rats after intracerebroventricular administration of oxytocin. Proc Natl Acad Sci USA 76:6661–6665
Richard P, Moos F, Belvin V, Freund-Mercier MJ (1985) Aminergic and peptidergic control of oxytocin secretion during suckling. In: Amico JA, Robinson AG (eds) Oxytocin: clinical and laboratory studies. Elsevier, Amsterdam, pp 154–166
Saydoff JA, Rittenhouse PA, van de Kar LD, Brownfield MS (1991) Enhanced serotonergic transmission stimulates oxytocin secretion in conscious male rats. J Pharmacol Exp Ther 257:95–99
Sofroniew M (1985) Vasopressin, oxytocin and their related neurophysins. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy, vol 4, part I. Elsevier, Amsterdam, pp 93–165
Stock S, Uvnäs-Moberg K (1988) Increased plasma levels of oxytocin in response to stimulation of the sciatic and vagal nerves and in response to touch and pinch in anaesthetized rats. Acta Physiol Scand 132:29–34
Svartengren J, Simonsson P (1990) Receptor binding properties of amperozide. Pharmacol Toxicol Suppl 1:8–11
Uvnäs-Moberg K, Widström AM, Nissen E, Björvell H (1990) Personality traits in women 4 days postpartum and their correlation with plasma levels of oxytocin and prolactin. J Psychosom Obstet Gynaecol 11:261–273
Uvnäs-Moberg K, Arn I, Theorell T, Jonsson CO (1991) Personality traits in a group of individuals with functional disorders of the gastrointestinal tract and their correlation with gastrin, somatostatin and oxytocin levels. J Psychosom Res 35:515–523
Uvnäs-Moberg K, Alster P, Hillegaart V, Ahlenius S (1992) Oxytocin reduces exploratory motor behaviour and shifts the activity towards the centre of the arena in male rats. Acta Physiol Scand (in press)
Verbalis JG, Stricker EM, Robinson AG, Hoffman GE (1991) Cholecystokinin activates C-fos expression in hypothalamic oxytocin and corticotropin-releasing hormone neurons. J Neuroendocrinol 3:205–213
Williams TDM, Carter DA, Lightman SL (1985) Sexual dimorphism in the posterior pituitary response to stress in rat. Endocrinology 116:738–740
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Uvnäs-Moberg, K., Alster, P. & Svensson, T.H. Amperozide and clozapine but not haloperidol or raclopride increase the secretion of oxytocin in rats. Psychopharmacology 109, 473–476 (1992). https://doi.org/10.1007/BF02247726
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DOI: https://doi.org/10.1007/BF02247726