The Vasopressin 1b Receptor Antagonist A-988315 Blocks Stress Effects on the Retrieval of Object-Recognition Memory

Abstract

Stress-induced activation of the hypothalamo-pituitary-adrenocortical (HPA) axis and high circulating glucocorticoid levels are well known to impair the retrieval of memory. Vasopressin can activate the HPA axis by stimulating vasopressin 1b (V1b) receptors located on the pituitary. In the present study, we investigated the effect of A-988315, a selective and highly potent non-peptidergic V1b-receptor antagonist with good pharmacokinetic properties, in blocking stress effects on HPA-axis activity and memory retrieval. To study cognitive performance, male Sprague-Dawley rats were trained on an object-discrimination task during which they could freely explore two identical objects. Memory for the objects and their location was tested 24 h later. A-988315 (20 or 60 mg/kg) or water was administered orally 90 min before retention testing, followed 60 min later by stress of footshock exposure. A-988315 dose-dependently dampened stressinduced increases in corticosterone plasma levels, but did not significantly alter HPA-axis activity of non-stressed control rats. Most importantly, A-988315 administration prevented stress-induced impairment of memory retrieval on both the object-recognition and the object-location tasks. A-988315 did not alter the retention of non-stressed rats and did not influence the total time spent exploring the objects or experimental context in either stressed or non-stressed rats. Thus, these findings indicate that direct antagonism of V1b receptors is an effective treatment to block stress-induced activation of the HPA axis and the consequent impairment of retrieval of different aspects of recognition memory.

Arginine Vasopressin and Arginine Vasopressin Receptor 1b Involved in Electroacupuncture-Attenuated Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Hepatectomy Rats

“…Nelivaptan (SSR149415) is a selective AVPR1b antagonist . Blockade of AVPR1b reduced the increase of ACTH and CORT .…”

Chronic Stress Reduces Nectin-1 mRNA Levels and Disrupts Dendritic Spine Plasticity in the Adult Mouse Perirhinal Cortex

“…Perirhinal neurons are activated when animals navigate through an environment with objects (Burke et al, 2012 ), and they play an essential role in various forms of recognition memory (Eichenbaum et al, 2007 ; Squire et al, 2007 ; Suzuki and Naya, 2014 ). In adult animals, chronic stress impairs performance in the novel object recognition task (Wang et al, 2011a ; Barsegyan et al, 2015 ; Franklin et al, 2018 ) that is dependent on the perirhinal cortex (Dere et al, 2007 ). In addition, chronic stress impairs temporal order memory (van der Kooij et al, 2014 ) that requires the functional connections among the perirhinal cortex, the hippocampus and the prefrontal cortex (Barker et al, 2007 ; Barker and Warburton, 2011 ).…”

“…As a major component of the parahippocampal region, the perirhinal cortex has both indirect and direct connections with the hippocampus (van Strien et al, 2009 ; Kealy and Commins, 2011 ) and plays an integral role in several key aspects of memory, especially recognition memory (Eichenbaum et al, 2007 ; Squire et al, 2007 ; Suzuki and Naya, 2014 ). Excitotoxic lesions of the perirhinal cortex lead to a selective loss of novel object recognition memory (Barker et al, 2007 ; Barker and Warburton, 2011 ), which is also compromised in animals subjected to chronic adult stress (Wang et al, 2011a ; Barsegyan et al, 2015 ; Franklin et al, 2018 ) or early-life stress (Reincke and Hanganu-Opatz, 2017 ). Intriguingly, lesions of the perirhinal cortex buffer acute stress-induced anxiety-related behavior (Schulz-Klaus, 2009 ), further indicating its involvement in stress-induced behavioral and cognitive deficits.…”

Control of Stress-Induced ACTH Secretion by Vasopressin and CRH: Additional Evidence

“…Considering this, we actually assumed that these drugs act on brain sites rather than the pituitary gland to control ACTH secretion. In addition, new V 1b antagonists have been developed [20,21] and may offer different pharmacokinetics and eventually longer-lasting effects that, in combination with SSR124453, could constitute a good alternative for long-lasting blockade of the HPA axis.…”