title: Selective blockade of 5-HT7 receptors facilitates attentional set-shifting in stressed and control rats.
abstract: Preclinical data demonstrate that the selective blockade of 5-HT7 receptors produces antidepressant-like behavioural effects. Although the involvement of 5-HT7 receptors in cognitive processes has been previously suggested, little is known about their role in the prefrontal cortex (PFC)-dependent processes that may be impaired in stress-related states. According to our previous study, repeated restraint stress induces the long-lasting cognitive impairment in a rat model of PFC-dependent attentional set-shifting task (ASST). Therefore, the first aim of the present experiments was to examine the impact of the selective 5-HT7 receptor antagonist, SB-269970, on ASST performance of stressed and control rats. Since the selective blockade of 5-HT7 receptors has been previously demonstrated to enhance the behavioural effects of antidepressants, the second goal was to examine the impact of the joint administration of inactive doses of SB-269970 and escitalopram in the ASST. SB-269970 (0.3 and 1mg/kg) given to stressed rats 30min before testing reversed the restraint-induced impairment of the extra-dimensional (ED) set-shifting ability. Additionally, SB-269970 (1mg/kg) also improved ED performance of the unstressed control group. Moreover, SB-269970, given at an inactive dose, enhanced the pro-cognitive efficacy of escitalopram. In conclusion, these results highlight the possibility that 5-HT7 receptor antagonism may represent a useful pharmacological approach in the treatment of frontal-like cognitive disturbances in stress-related psychiatric disorders.
authors.affiliation: Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland. nikifor@if-pan.krakow.pl
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Nikiforuk
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012149:Restraint, Physical; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012718:Set, Psychology; D013312:Stress, Physiological / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D015283:Citalopram; D010636:Phenols; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D013449:Sulfonamides; C404922:SB 269970; C104425:serotonin 7 receptor