Abstract
A wide body of evidence suggests that 5-HT7 receptors are implicated in a variety of central nervous system functions, including control of learning and memory processes. According to recent preclinical data, the selective blockade of these receptors may be a potential target for cognitive improvement in schizophrenia. The first aim of the present study was to evaluate the effects of the selective 5-HT7 receptor antagonist, SB-269970, and the antipsychotic drug with a high affinity for 5-HT7 receptors, amisulpride, on ketamine-induced deficits in attentional set-shifting and novel object recognition tasks in rats. Because the role of 5-HT7 receptor blockade in ameliorating positive and negative symptoms of schizophrenia remains equivocal, the second aim of these experiments was to examine the effectiveness of SB-269970 and amisulpride in reversing ketamine-induced deficits in prepulse inhibition of the startle reflex and in social interaction test in rats. The study revealed that acute administration of SB-269970 (1 mg/kg) or amisulpride (3 mg/kg) ameliorated ketamine-induced cognitive inflexibility and novel object recognition deficit in rats. Both compounds were also effective in attenuating ketamine-evoked disruption of social interactions. In contrast, neither SB-269970 nor amisulpride affected ketamine-disrupted prepulse inhibition or 50 kHz USVs accompanying social behaviour. In conclusion, antagonism of 5-HT7 receptors may represent a useful pharmacological approach in the treatment of cognitive deficits and some negative symptoms of schizophrenia.
Highlights
A wide body of evidence supports a role for 5-HT7 (5hydroxytryptamine 7, serotonin 7) receptors in the modulation of diverse processes of the central nervous system [1,2,3]
The present study revealed that acute administration of the selective 5-HT7 receptor antagonist, SB-269970, and amisulpride ameliorated ketamine-induced cognitive inflexibility and novel object recognition deficit in rats
The ketamine-induced reduction in ultrasonic vocalisations was not reversed by either treatment
Summary
A wide body of evidence supports a role for 5-HT7 (5hydroxytryptamine 7, serotonin 7) receptors in the modulation of diverse processes of the central nervous system [1,2,3]. While the involvement of 5-HT7 receptors in modulating cognitive processes under physiological conditions remains poorly understood [4,5], recent data suggest that 5-HT7 antagonists are effective in overcoming cognitive impairments in an animal model of schizophrenia involving blockade of N-methyl-D-aspartate receptors (NMDARs) [6,7,8,9]. Cognitive flexibility, a component of executive control subserved by the prefrontal cortex (PFC), can be evaluated in rodents in the attentional set-shifting task (ASST) [16] In this paradigm, rats must select a bowl containing a food reward based on the ability to discriminate the odours and the media covering the bait. The animals’ performance at the ED stage is regarded as an index of cognitive flexibility
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
