Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze

Abstract

The 5-HT 2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats) and low (spontaneously hypertensive rats, SHR) anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing) increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing) failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT 2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage) was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT 2B/2C receptors.

Effects of ethanol on locomotor and anxiety-like behaviors and the acquisition of ethanol intake in Lewis and spontaneously hypertensive rats

“…It should be recalled that, as previously mentioned, SHR and LEW rats differ in basal anxiety levels, the former presenting least anxiety-related behavior and the latter showing most anxiety-related behavior. In this context, it is interesting to note that in our previous studies (Takahashi et al, 2001;Vendruscolo et al, 2003) using the same models and same strain of animals, but testing other anxiolytics, such as diazepam, clordiazepoxide and NKP-608, a lack of anxiolytic-like effects of these drugs was seen in the LEW strain. We suggested that the high-anxiety profile of these rats may be resistant to these drugs.…”

Two inbred rat strains contrasting for anxiety-related behaviors show similar levels of defensive responses to cat odor

“…In this study, the LEW and SHR strains, which are known to differ in several behavioral tests of anxiety/emotionality [18-25], displayed similar anxiety-like responses when evaluated in the COT. All groups highly avoided the collar and the environment containing the cat odor.…”

“…These strains, however, do not differ in their activity levels in either novel or familiar environments [18-25] but pharmacological studies indicate that they respond differently to the anxiolytic effects of benzodiazepines [18,19,21]. The anxiety-related differences between LEW and SHR were found to be due to genetic effects [20,22,24].…”

Chronic aortic denervation decreases anxiety and impairs social memory in rats

“…However, the open arm entries were markedly increased and also the time spent in open arms was elevated in bAD rats, compared to CTRL-and SHAM rats, an indication of decreased anxiety-like behaviour. Also SHR are less fearful than normotensive rats in the elevated plus-maze test (Durand et al 1999;Takahashi et al 2001), though the performance of active avoidance tasks by SHR is thought to be influenced by a slower habituation, hyperactivity, and hyperreactivity (Scriabine et al 1989;Wultz et al 1990). Increased reactivity could be observed especially during exposure to novel stimuli (Sagvolden et al 1992).…”

“…The combination of different models of hypertension with a variety of behavioural, learning, and memory tasks additionally impedes comparison of the findings. For instance, renal hypertensive rats show anxiogenic-like behaviour in an elevated plus-maze test (Srinivasan et al 2003), while spontaneous hypertensive rats (SHR), another model of hypertension, have decreased levels of anxiety in an open-field test (Durand et al 1999) but also in an elevated plus-maze test (Durand et al 1999;Takahashi et al 2001). Furthermore, chronic hypertension evoked by aortic coarctation leads, ten months after surgery, to no impairment in spatial learning and memory when observing the rats during a repeated-acquisition water maze task (Kadish et al 2001).…”