Sertindole restores attentional performance and suppresses glutamate release induced by the NMDA receptor antagonist CPP

Abstract

These findings show that the ameliorating effects of sertindole and clozapine on NMDA receptor dependent attention deficit is associated with suppression in GLU release in the mPFC. This supports the proposal that suppression in GLU release might be a target for the development of novel drugs aimed at counteracting some aspects of cognitive deficits of schizophrenia.

Serotoninergic and dopaminergic modulation of cortico-striatal circuit in executive and attention deficits induced by NMDA receptor hypofunction in the 5-choice serial reaction time task

“…In the 5CSRT task clozapine, olanzapine and low doses of sertindole prevented R-CPP-induced impairment of correct responses and impulsivity but had no effects on compulsivity (Baviera et al, 2008; Carli et al, 2011a,b) resembling the effect of M100907. These antipsychotics block with high affinity 5-HT 2A receptors (Arnt and Skarsfeldt, 1998), which likely played a major role in their effects on attention.…”

“… Data from: Ceglia et al, 2004; Calcagno et al, 2006, 2009; Carli et al, 2011a,b; Agnoli et al, 2013 .↑, increase; ↓, decrease .…”

“…Data from:a Mirjana et al, 2004 ,b Ceglia et al, 2004 ,c Carli et al, 2006a ,d Calcagno et al, 2006 ,e Calcagno et al, 2009 ,f Pozzi et al, 2011 ,g Baviera et al, 2008 ,h Carli et al, 2011b ,i Carli et al, 2011a .↓, decrease; ↑, increase; 0, reversal of R-CPP-induced effect .…”

Schedule-induced polydipsia as a model of compulsive behavior: neuropharmacological and neuroendocrine bases

“…However, to date, no studies have explored the effects of selective noradrenalin reuptake blockers such as atomoxetine in SIP. Finally, although there are several studies that related blockade of glutamate NMDA receptors with compulsive responding such as the perseverative responses on the 5-CSRT task (Carli et al 2006(Carli et al , 2011a, the studies on the administration of NMDA receptor antagonists have reported different effects on SIP. The administration of phencyclidine during acquisition and maintenance decreased SIP behavior (Didriksen and Christensen 1994).…”

“…Experimental measures used to assess compulsive behavior in animal models have included: stereotypy, signal attenuation, retarded extinction in reversal learning tasks (for review, see Boulougouris et al 2009;Fineberg et al 2011), compulsive drug seeking in self-administration (Belin et al 2008), perseverative responses on the sustained attention 5-choice serial reaction time (5-CSRT) task (Carli et al 2006(Carli et al , 2011a, and adjunctive or displacement behavioral models (Woods-Kettelberger et al 1997).…”