Modulation of anxiety behavior in the elevated plus maze using peptidic oxytocin and vasopressin receptor ligands in the rat

Abstract

Oxytocin (OT) and arginine vasopressin (AVP), in their capacities as neuromodulators, are believed to play an important role in mood control, including regulation of the anxiety response. In the present study, the contributions of oxytocin and vasopressin receptor modulation to anxiety-like behaviors were examined in male Sprague-Dawley rats. The behavioral effects of the OT receptor agonist, carbetocin (intracerebroventricular, intravenous and intraperitoneal routes), the AVP receptor agonist desmopressin (intravenous route), and the OT/AVP(1A) receptor antagonist atosiban (intravenous route) were evaluated in the elevated plus maze. The benzodiazepine diazepam was included as a positive control. Central but not systemic administration of carbetocin produced pronounced anxiolytic-like behavioral changes comparable to those measured following systemic diazepam treatment. The anxiolytic efficacy of carbetocin was maintained following 10 days of once-daily treatment, contrasting with the effects of diazepam which were no longer distinguishable from saline treatment. Systemic administration of desmopressin produced anxiogenic-like effects whereas systemic atosiban produced anxiolytic-like effects. Co-administration of desmopressin with atosiban resulted in saline-like behavioral responses, implicating an AVP(1A) receptor mechanism in the anxiolytic and anxiogenic effects of these neuropeptides following systemic administration. A peripherally-mediated antidiuretic effect of desmopressin on water consumption was also demonstrated. These results highlight the potential therapeutic utility of AVP(1A) receptor blockade in the modulation of anxiety-related behaviors; AVP(1A) receptor blockade appears to be a more promising pharmacological target than does OT receptor activation following systemic drug administration.

Effects of atosiban on stress-related neuroendocrine factors

“…It should be noted that, to our knowledge, no data are available on the permeability of the blood-brain barrier to atosiban. However, centrally mediated effects of peripherally injected atosiban have also been reported by other authors (Broadbear et al 2011, Mak et al 2012, indicating that the drug can reach at least certain regions of the brain. Several areas in the brain called circumventricular organs, including parts of the hypothalamus, are not protected by the blood-brain barrier (Bartanusz & Jezová 1992).…”

“…Oxytocin and vasopressin receptors have been implicated in the regulation of anxiety and stress responses (Mak et al 2012, Bowen & McGregor 2014. In contrast to the knowledge regarding the actions of atosiban on reproductive functions, the information available on its effects on the brain is very limited (Broadbear et al 2014).…”

Oxytocin und die suchterhaltenden Mechanismen der Alkoholabhängigkeit

“…In unterschiedlichen Tests war der anxiolytische Effekt von Oxytocin mit dem eines Benzodiazepins vergleichbar [47]. Oxytocin bewirkt ebenso wie ein Benzodiazepin Anxiolyse, nach 10 Tagen trat jedoch bei Diazepam in einer Tierstudie ein Gewöhnungseffekt ein, der bei Oxytocin nicht zu verzeichnen war [48]. Wenn dieser ausbleibende oder im Vergleich zu Benzodiazepinen schwächere Gewöhnungseffekt in weiteren Studien bestätigt wird, bleibt festzustellen, ob diese Eigenschaft auch eine potenzielle Abhängigkeitsent-wicklung von Oxytocin beeinflussen würde.…”

Chronic methamphetamine treatment induces oxytocin receptor up-regulation in the amygdala and hypothalamus via an adenosine A2A receptor-independent mechanism

“…The reason that we did not observe any modulation of this MAP-induced upregulation in A 2A KO mice might be due to the low expression of A 2A in these brain regions. Although, there is some evidence of A 2A expression in the amygdala (Hume et al , 1996, Mak et al , 2012 and hypothalamus (Kokoshka et al , 1998, Volkow et al , 2009 It is important to point out here that, despite its significant contribution towards understanding the mechanisms underlyining the effects of drugs of abuse, full developmental 18 KO mouse technology does not come without limitations (see review by Yoo et al, (2012)). …”