Disruption of the Prepulse Inhibition of the Startle Reflex in Vasopressin V1b Receptor Knockout Mice: Reversal by Antipsychotic Drugs

Abstract

In the present study, we investigated whether mice lacking the arginine vasopressin (AVP) V1b receptor (V1bR) exhibit deficits of prepulse inhibition (PPI) of the startle reflex, reminiscent of the sensorimotor gating deficits observed in a large majority of schizophrenic patients. V1bR knockout (KO) mice displayed significantly reduced levels of PPI of the startle reflex. In addition to PPI deficits, V1bR KO mice showed increased acoustic startle response. However, acoustic startle response was not significantly correlated to the PPI of the startle reflex in V1bR KO mice. V1bR KO mice also showed a decrease in basal levels of extracellular dopamine (DA) in the medial prefrontal cortex, which is thought to be an important brain region for PPI. Moreover, PPI deficits observed in the V1bR KO mice are significantly reversed by atypical antipsychotics such as risperidone and clozapine but not by a typical neuroleptic haloperidol, like in schizophrenic patients. By contrast, we did not observe any significant differences between V1bR KO mice and wild-type mice in the open-field, light/dark, elevated plus maze, and forced swimming tests. The results of the present study indicate that V1bR may be involved in the regulation of PPI of the startle reflex. The V1bR has been considered an important molecular target for the development of antipsychotic drugs.

Attenuated stress-induced catecholamine release in mice lacking the vasopressin V1b receptor

“…The method is used for evaluating anti-depressant drugs such as serotonine-selective reuptake inhibitors or serotonine-noradrenaline reuptake inhibitors. Our results indicated that the basal FST immobility time of V 1 bR Ϫ/Ϫ mice did not differ from that of wild-type mice, which is consistent with the results of previous reports where V 1b R Ϫ/Ϫ mice were used (3,23). Furthermore, in the present study we demonstrated that the FST immobility time of V 1b R Ϫ/Ϫ mice did not differ from that of wild-type mice, even after exposure to chronic isolation stress.…”

New Topics in Vasopressin Receptors and Approach to Novel Drugs: Role of the Vasopressin Receptor in Psychological and Cognitive Functions

“…Moreover, PPI deficits observed in the V1bR KO mice are significantly reversed by atypical antipsychotics such as risperidone and clozapine but not by the typical neuroleptic haloperidol (57). Our results are in good agreement with clinical data obtained from schizophrenic patients.…”

Vasopressin V1a and V1b Receptors: From Molecules to Physiological Systems

“…Differences in strain background, testing procedures, and situations may account for this discrepancy. Also, their and our groups reported that V1bR-KO mice show normal anxiety levels in the elevated plus-maze and light/dark tests (133,533). Moreover, using a marble-burying test, we confirmed that there was no significant difference between V1bR-KO mice and WT mice in the number of marbles buried (132), whereas V1aR-KO mice buried significantly fewer marbles than WT mice did (135).…”

“…V1a receptor signaling and V1b receptor signaling in the LS, amygdala, and hippocampal areas are critical in the regulation of anxiety-and depression-related behaviors. However, V1aR-KO and V1bR-KO mice performed normally in the forced swimming test (49,133,135,532). Additionally, V1bR-KO mice displayed a normal anxiety-like response in the elevated plus-maze and light/dark tests (133,533).…”