Arginine Vasopressin‐lnduced Sensitization in Brain: Facilitated Inositol Phosphate Production Without Changes in Receptor Number

Abstract

Arginine vasopressin (AVP) has been shown to have a unique sensitization effect whereby repeated injection of AVP into a lateral cerebral ventricle or a mediobasal region of the rat forebrain below the lateral septum and including the anterior hypothalamus referred to as the ventral septal area, causes enhanced motor responses to the ligand. To elucidate possible neuronal mechanisms responsible for AVP sensitization, 1) we determined the dose and the time required for the development and expression of AVP sensitization, and 2) we tested the hypotheses that AVP sensitization may result in a) alteration of septal AVP V1 receptor affinity or number, and/or b) alteration of septal AVP V1 receptor signal transduction (phosphatidylinositol hydrolysis) mechanisms. Our behavioral data show that the magnitude of AVP sensitization varies with dose and time, and the effect is dependent on the time interval between injections, in that an initial intracerebroventricular AVP injection enhances the sensitivity of the animals to the motor effects of similar AVP injections given 6 h to 6 days later but not to injections given hourly or weekly. No changes in septal AVP binding site density and affinity, as measured by [3H]AVP binding to septal synaptic plasma membrane, were found in sensitized animals; [3H]inositol monophosphate stimulation in response to AVP in septal slices, however, was found to be significantly enhanced. This enhanced [3H]inositol monophosphate stimulation appears specific to a V1-type receptor because it was significantly reduced in the presence of the V1 receptor antagonist, d(CH2)5Tyr(Me)AVP, and was not found using oxytocin or the V2 receptor agonist, DDAVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed effect of the vasopressin metabolite VP4-8 on the social memory of sexually naive male rats

“…Pretreatment with vasopressin also sensitised the central effects of vasopressin on the startle response, and on blood pressure and sympathetic nerve activity (LeBrun et al 1989;Pelton et al 1997). The 2-day interval used in our experiments falls within the time window for sensitised vasopressin responses, which lasts from 6 h to 6 days after pretreatment (Poulin and Pittman 1993). Furthermore, as in other studies, the treatment inducing the sensitisation had no acute effect (Poulin et al 1995;Pelton et al 1997).…”

“…Vasopressin sensitisation is accompanied by an increased inositol phosphate response to vasopressin in septal slices, indicating an enhanced responsiveness of vasopressin receptors in the septum (LeBrun et al 1990;Poulin and Pittman 1993). Sensitisation of vasopressin responses can also be induced by treatments known to induce endogenous vasopressin release, such as hypertonic saline and haemorrhage (Burnard et al 1983).…”

Alteration of the physiological responses to indomethacin by endotoxin tolerance in the rat: a possible role for central vasopressin.

“…The present study was conducted on the premise that exposure of ventral septal AVP receptors to their endogenous ligand, such as we have shown to occur during tolerance to LPS (Wilkinson & Kasting, 1990b;Wilkinson et al 1992), would result in sensitization of the receptor in a manner previously described (Poulin & Pittman, 1993a). We have also determined, using both receptor antagonists (Wilkinson & Kasting, 1989) and push-pull perfusion studies (Wilkinson & Kasting, 1993) .…”

“…Unlike many neurotransmitter-receptor systems which downregulate upon exposure to their ligand, VSA receptors become sensitized when intermittently exposed to AVP or oxytocin (Poulin & Pittman, 1993a). That is, the responses to exogenous AVP are enhanced if the animal is pretreated centrally with exogenous peptide or if endogenous release of AVP (or oxytocin) is evoked by stimuli such as haemorrhage, hypertonic saline treatment (Burnard, Pittman & Veale, 1983) or fever (Poulin & Pittman, 1993 b).…”

Activation of multiple intracellular transduction signals by vasopressin in vasopressin‐sensitive neurones of the rat supraoptic nucleus

“…Little is known about vasopressin-induced intracellular transduction pathways in the brain. It has been reported that vasopressin increases the production of inositol phosphates in the hippocampus (Diaz-Brinton et al 1994;Stephens & Logan, 1986), in septum (Shewey & Dorsa, 1988;Lebrun et al 1990;Poulin & Pittman, 1993) and in dorsomedial medulla oblongata (Moratalla et al 1988). In other studies, the vasopressin failed to activate adenylate cyclase (AC) in hippocampus and septum (Barberis, 1983;Dorsa et al 1983;Audigier & Barberis, 1985;Brinton & McEwen, 1989).…”