Effects of the selective 5-HT7 receptor antagonist SB-269970 and amisulpride on ketamine-induced schizophrenia-like deficits in rats.
Agnieszka Nikiforuk, Tomasz Kos, Katarzyna Fijał, Małgorzata Hołuj, Dominik Rafa, Piotr Popik
Index: PLoS ONE 8(6) , e66695, (2013)
Full Text: HTML
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.
Related Compounds
Related Articles:
2000-02-10
[J. Med. Chem. 43(3) , 342-345, (2000)]
Characterization of SB-269970-A, a selective 5-HT(7) receptor antagonist.
2000-06-01
[Br. J. Pharmacol. 130(3) , 539-48, (2000)]
[(3)H]-SB-269970--A selective antagonist radioligand for 5-HT(7) receptors.
2000-05-01
[Br. J. Pharmacol. 130(2) , 409-17, (2000)]
8-OH-DPAT acts on both 5-HT1A and 5-HT7 receptors to induce hypothermia in rodents.
2004-03-08
[Eur. J. Pharmacol. 487(1-3) , 125-32, (2004)]
2012-04-01
[Br. J. Pharmacol. 165(7) , 2191-202, (2012)]