Intracerebroventricular oxytocin administration in rats enhances object recognition and increases expression of neurotrophins, microtubule‐associated protein 2, and synapsinI

Abstract

Brain oxytocin regulates a variety of social and affiliative behaviors and affects also learning and memory. However, mechanisms of its action at the level of neuronal circuits are not fully understood. The present study tests the hypothesis that molecular factors required for memory formation and synaptic plasticity, including brain-derived neurotrophic factor, neural growth factor, nestin, microtubule-associated protein 2 (MAP2), and synapsin I, are enhanced by central administration of oxytocin. We also investigated whether oxytocin enhances object recognition and acts as anxiolytic agent. Therefore, male Wistar rats were infused continuously with oxytocin (20 ng/µl) via an osmotic minipump into the lateral cerebral ventricle for 7 days; controls were infused with vehicle. The object recognition test, open field test, and elevated plus maze test were performed on the sixth, seventh, and eighth days from starting the infusion. No significant effects of oxytocin on anxious-like behavior were observed. The object recognition test showed that oxytocin-treated rats significantly preferred unknown objects. Oxytocin treatment significantly increased gene expression and protein levels of neurotrophins, MAP2, and synapsin I in the hippocampus. No changes were observed in nestin expression. Our results provide the first direct evidence implicating oxytocin as a regulator of brain plasticity at the level of changes of neuronal growth factors, cytoskeletal proteins, and behavior. The data support assumption that oxytocin is important for short-term hippocampus-dependent memory.

Oxytocin in General Anxiety and Social Fear: A Translational Approach

“…In contrast, in ovariectomized, steroid-treated female rats, 5 days of icv OXT (10 ng/hour) reduced anxiety levels and stress-induced c-Fos activation in relevant brain regions (66,72). In support of such sex differences, 7 days icv OXT (20 ng/hour) in male rats did not affect anxiety-related behavior (69).…”

“…However, relevant basic studies are rare, and those performed reveal that chronic OXT effects strongly depend on the dose and duration of application, are likely to vary between male and female subjects (65)(66)(67)(68)(69)(70)(71)(72), and are dependent upon the innate level of anxiety (65). For example, in male mice, chronic icv infusion of OXT (10 ng/hour) over 2 weeks induced a robust increase in anxiety-related behavior in two independent behavioral tests, whereas a tenfold lower dose did not alter anxiety (67).…”

Binding to and Inhibition of Insulin-Regulated Aminopeptidase by Macrocyclic Disulfides Enhances Spine Density

“…Therefore, the potential procognitive effects of IRAP inhibitors may be mediated by increases in the levels and prolongation of activity of substrates including oxytocin. Oxytocin has recently been reported to enhance learning and memory, particularly in the novel recognition paradigm in rodents (Gard et al, 2012;Havranek et al, 2015). Although the effect of oxytocin on hippocampal dendritic spine density is not known, its effect on glucose uptake is documented.…”

The influence of offspring, parity, and oxytocin on cognitive flexibility during the postpartum period

“…The mPFC abundantly expresses oxytocin receptors (OT-R; Insel and Shapiro, 1992; Liu et al, 2005; Smeltzer et al, 2006; Nakajima et al, 2014; Mitre et al, 2016) and receives long range axonal projections from OT producing neurons in the hypothalamus (Sofroniew, 1983; Knobloch et al, 2012). In addition, OT has been shown to mediate the motherhood-induced enhancement in spatial memory (Tomizawa et al, 2003) and research in non-parous animals has shown that OT can influence various aspects of learning and memory (Gur et al, 2014; Havranek et al, 2015), including cognitive flexibility which is impaired in oxytocin receptor (OT-R) knockout mice (Sala et al, 2011; Chini et al, 2014). However, no previous work has investigated whether OT contributes to improved cognitive flexibility during the postpartum period.…”