The antagonists of serotonin 5-HT7 receptors have been demonstrated to ameliorate cognitive impairments in pharmacological animal models of schizophrenia that involve blockade of N-methyl-D-aspartate receptors (NMDARs). The administration of NMDAR antagonists evokes a broad range of cognitive deficits, including a loss of impulse control. The involvement of 5-HT7 receptors in the modulation of impulsivity has been recently suggested but has not been studied in great detail. The aim of the present study was to examine the effect of a selective 5-HT7 receptor antagonist SB-269970 on a measure of impulsive action, i.e., premature responding on the five-choice serial reaction time task (5-CSRTT) in rats. The antagonist of 5-HT2A receptor M100,907 was used as a positive control. The efficacies of both compounds were assessed in conditions of increased impulsivity that were produced by the administration of the NMDAR antagonist MK-801 or/and non-drug stimuli, i.e., using variable inter-trial intervals (vITIs). To examine the general ability of SB-269970 to counteract the MK-801-induced impairments, a discrete paired-trial delayed alternation task in a T-maze was employed. MK-801 significantly increased the number of premature responses in 5-CSRTT, and this effect was abolished by the administration of M100,907 (0.5 mg/kg) and SB-269970 (1 mg/kg). In addition, M100,907, but not SB-269970, reduced premature responding in the prolonged ITI trials. Both M100,907 and SB-269970 attenuated MK-801-induced working memory impairment in a T-maze. The present study demonstrated the efficacy of SB-269970 against MK-801-induced premature responding in the 5-CSRTT. This anti-impulsive action may offer additional benefits to the cognitive-enhancing effects of pharmacological blockade of 5-HT7 receptors.
Keywords: 5-CSRTT; 5-HT2A receptor; 5-HT7 receptor; Impulsivity; SB-269970.
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