Effects of the selective 5-HT7 receptor antagonist SB-269970 and amisulpride on ketamine-induced schizophrenia-like deficits in rats.

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.

• Authors: Agnieszka Nikiforuk, Tomasz Kos, Katarzyna Fijał, Małgorzata Hołuj, Dominik Rafa, Piotr Popik
• Journal: PloS one (PLoS One) Vol. 8 Issue 6 Pg. e66695 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23776692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phenols
• Receptors, Serotonin
• SB 269970
• Serotonin Antagonists
• Sulfonamides
• serotonin 7 receptor
• Ketamine
• Sulpiride
• Amisulpride

Topics

• Amisulpride
• Animals
• Ketamine (toxicity)
• Male
• Phenols (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Receptors, Serotonin (metabolism)
• Schizophrenia (chemically induced, drug therapy)
• Serotonin Antagonists (therapeutic use)
• Sulfonamides (therapeutic use)
• Sulpiride (analogs & derivatives, therapeutic use)