Nov 21, 2012

Behavioural and neuroplastic properties of chronic lurasidone treatment in serotonin transporter knockout rats

The International Journal of Neuropsychopharmacology
Alessia LuoniMarco A Riva

Abstract

Second-generation antipsychotics (SGA) are multi-target agents widely used for the treatment of schizophrenia and bipolar disorder that also hold potential for the treatment of impaired emotional control, thanks to their diverse receptor profiles as well as their potential in modulating neuroadaptive changes in key brain regions. The aim of this study was thus to establish the ability of lurasidone, a novel SGA characterized by a multi-receptor signature, to modulate behavioural and molecular defects associated with a genetic model of impaired emotional control, namely serotonin transporter knockout (SERT KO) rats. At behavioural level, we found that chronic lurasidone treatment significantly increased fear extinction in SERT KO rats, but not in wild-type control animals. Moreover, at molecular level, lurasidone was able to normalize the reduced expression of the neurotrophin brain-derived neurotrophic factor in the prefrontal cortex of SERT KO rats, an effect that occurred through the regulation of specific neurotrophin transcripts (primarily exon VI). Furthermore, chronic lurasidone treatment was also able to restore the reduced expression of different GABAergic markers that is present in these animals. Our results show that ...Continue Reading

Mentioned in this Paper

Prefrontal Cortex
Exons
Recombinant Brain-Derived Growth Factors
Brain-Derived Neurotrophic Factor Measurement
Serotonin transporter
Serotonectin
Neurotrophic factor
Lurasidone
Bipolar Disorder
BDNF gene

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