Effects of aripiprazole, olanzapine, and haloperidol in a model of cognitive deficit of schizophrenia in rats: relationship with glutamate release in the medial prefrontal cortex

Abstract

The data confirm that excessive GLU release in the mPFC is associated with attentional deficits. Thus, suppression of GLU release may be a target for the development of novel antipsychotic drugs with greater effect on some aspects of cognitive deficits.

Effects of Risperidone on Learning and Memory in Naive and MK-801-Treated Rats

“…Controver-sially, a recent study found that excessive glutamate release in the medial prefrontal cortex is associated with attentional deficits. The study confirmed that the suppression of glutamate release may be a target for the development of novel antipsychotic drugs with greater effect on some aspects of cognitive deficits [5] .…”

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

“…Lister Hooded rats were preferred for behavioural studies as they reach high levels of performance after training on the 5CSRT task. On the other hand, CD rats were preferred for microdialysis as previous studies were done on this strain (Calcagno et al 2009;Calcagno et al 2006;Ceglia et al 2004) and no gross differences in the response to intracortical CPP were noted between Lister Hooded and CD rats (Carli et al 2010).…”

Serotonin in antipsychotic drugs action

“…For example, olanzapine decreased both basal and stimulated extracellular 5-HT levels in the medial prefrontal cortex [93,95,97,103], while other studies report either no changes in the medial prefrontal cortex, hippocampus, nucleus accumbens and hypothalamus [93,99,100,[103][104][105] or even an increase in the caudate-putamen [103] Similar figuers were reckoned for haloperidol and aripiprazole. Haloperidol is reported to decrease both basal and stimulated extracellular 5-HT levels in the medial prefrontal cortex in a number of studies [93,94,96,97,104,105]. Other studies, however, show that it did not change extracellular 5-HT levels neither in the medial prefrontal cortex, hippocampus or nucleus accumbens [93,99,100,106,107].…”

“…Haloperidol is reported to decrease both basal and stimulated extracellular 5-HT levels in the medial prefrontal cortex in a number of studies [93,94,96,97,104,105]. Other studies, however, show that it did not change extracellular 5-HT levels neither in the medial prefrontal cortex, hippocampus or nucleus accumbens [93,99,100,106,107]. One study showed that haloperidol increases extracellular 5-HT levels in frontal cortex [108].…”

“…Wistar rats accounted for 50% of the 24 studies with rats. Twelve studies used Sprague-Dawley rats and one study was carried out using Lister hodeed rats [93]. Two studies were carried out using a 14 days treatment schedule (continous olanzapine or haloperdol treatment using osmotic pumps [94,95]) while the remainig 25 studies were performed in single dose.…”