Wistar-Kyoto rats are sensitive to the hypolocomotor and anxiogenic effects of mCPP.

Abstract

Wistar-Kyoto (WKY) rats, but not spontaneously hypertensive rats (SHRs), are insensitive to the acute hypolocomotor and anxiogenic effects of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram, in elevated plus-maze tests. Several observations suggest that these strain-dependent effects involve postsynaptic serotonin (5-HT) receptors. In keeping with the recent finding that citalopram-elicited anxiety in Sprague-Dawley rats, as measured in the social interaction test, involves 5-HT(2C) receptor stimulation, we tested the hypothesis that this receptor is prone to subsensitivity in WKY rats, compared to SHRs. Thus, we first examined the acute behavioural effects of the 5-HT(2B/2C) receptor agonist, mCPP, in SHRs and WKY rats exposed to an elevated plus-maze; in addition, because WKY rats display anxiety and hypolocomotion, compared to SHRs, we next used the 5-HT(2B/2C) receptor antagonist, SB-206553, to test whether 5-HT(2C) receptors are tonically active in WKY rats. The results confirmed that WKY rats and SHRs differ in locomotor activity and anxiety-related behaviours, and showed that pretreatment with mCPP decreased locomotion in both strains. In contrast, the strains differed with respect to mCPP-elicited anxiety, as WKY rats were sensitive to the lowest dose of mCPP, while only the highest dose increased anxiety in SHRs. Finally, elevated plus-maze behaviours of SHRs and WKY rats were found to be insensitive to SB-206553 pretreatment. This study therefore suggests that 5-HT(2C) receptors (at least those which mediate mCPP-induced hypolocomotion and anxiety) are neither desensitized nor tonically active in WKY rats.