Anxiety and Stress Responses in Female Oxytocin Deficient Mice

Abstract

Oxytocin is believed to attenuate the response of the hypothalamic-pituitary-adrenal axis to stress and to be anxiolytic. Stressors with a psychological component evoke both central and peripheral secretion of oxytocin in laboratory rodents. Oxytocin gene deletion mice provide a novel way to understand the role of oxytocin in stress and anxiety-related behaviours. We present our experience with female oxytocin deficient mice that were tested in an elevated plus maze (EPM), a behavioural test of anxiety, or exposed to psychogenic stressors (platform shaker or novel environment). Oxytocin-deficient mice not only displayed more anxiety-related behaviour, but also released more corticosterone after a psychogenic stressor and manifested greater stress-induced hyperthermia compared to wild-type mice. The diurnal variation of corticosterone and the response of corticosterone to corticotropin-releasing factor were not significantly different between genotypes. We also measured Fos-immunoreactive protein, an index of neuronal activation, in the medial amygdala of female mice after EPM testing. The medial amygdala is important for processing of psychogenic stress and anxiety and also contains oxytocin pathways and oxytocin receptors. The expression of Fos in the medial amygdala of mice not exposed to the EPM was not different between genotypes. Following EPM exposure, Fos expression was greater in oxytocin null compared to wild-type mice. Our findings support the hypothesis that central oxytocin is anxiolytic, and attenuates the stress response to psychogenic provocation in female mice.

Plasma oxytocin levels and anxiety in patients with major depression

“…Central OT pathways are believed to facilitate anxiolysis and to attenuate the response of the HPA axis to psychogenic stressors. The medial amygdalia may be an important region for OT actions that govern a variety of social and stress behaviours (Amico et al, 2004). In major depression there is an upregulation in the HPA axis, which in turn down-regulates the 5-HT1A receptors and the activity of serotonin.…”

“…Hormones classically confined to the magnocellular-neurohypophysial system are found in the parvocellularlong portal system and are known to be implicated in the hypophysiotropic control of ACTH release. Apart from its presence in the hypothalamus, OT is found in several other brain regions (e.g., bed nucleus of the striae terminalis, central and medial nuclei of the amygdala, septum, hippocampus), suggesting that it has a role in neurotransmission, psychogenic stress and anxiety (Amico et al, 2004).…”

Mother–infant bonding and the evolution of mammalian social relationships

“…For completely novel stimuli, such as strange males or newly born offspring, overcoming neophobia is also a necessary prelude to forming new relationships. OT release is significant in this context too, since it is noteworthy that OT knockout mice exhibit altered levels of anxiety (Mantella et al 2003;Amico et al 2004) and intracerebroventricular (icv) administration of oxytocin receptor antagonists increases anxiety in female rats (Neumann et al 2000).…”

Intergenerational effects of cocaine on maternal aggressive behavior and brain oxytocin in rat dams

“…In addition to an association of oxytocin with MA, the stress response has also been strongly associated with oxytocin (Callahan et al 1989;Uvnas-Moberg et al 1994;Jezova et al 1995;Nishioka et al 1998;Uvnas-Moberg 1998;Neumann et al 2001;Amico et al 2004), a relationship that has been increasingly studied over the years. Oxytocin neurons are activated in response to various types of stressful stimuli (Ludwig 1998;Neumann 2002), and recent work has suggested the presence of an oxytocin-mediated, parasympathetically driven "anti-stress" system (Uvnas-Moberg 1997).…”