br Experimental procedures br Results br Discussion The resu

Experimental procedures
Results
Discussion The results demonstrate that anti-SVG-30 produced a dose-dependent DL-α-Hydroxyglutaric acid disodium salt sale in the duration of conditioned freezing, increased the level of elevated open arm exploration, and increased the amount of time spent in an open field. Hence, antagonism of CRF2 receptors produces a consistent anxiolytic-like behavioral profile in a number of different animal anxiety models. In addition, a behaviorally effective dose of anti-SVG-30 (10.0 μg) had no significant effects on locomotor activity. Although higher doses of anti-SVG-30 were not tested for their potential intrinsic behavioral effects, current results suggest that antagonism of CRF2 receptors, at a dose effective in attenuating freezing and increasing behavioral exploration in opened or unprotected areas, is not due to an antagonist-induced increase in motor behavior. The anxiolytic-like responses produced by anti-SVG-30 suggests that CRF2 receptors mediate not only the elicitation of anxiety behavior induced by prior stress, i.e. conditioned freezing, but also unconditioned anxiety behavior induced by exposure to the unfamiliar environment of the elevated plus maze and defensive-withdrawal test. Thus, behavioral differences reported in mice tested in the elevated plus maze after administration of anti-SVG-30 (see Introduction) [42] do not appear to be a consequence of whether anxiety testing occurred with or without prior exposure to stress. It should be indicated that we failed to detect an anti-SVG-30 induced increase in anxiety using the elevated plus maze test as reported previously (see Fig. 3a in Ref. [27]). In that study, mice treated with an i.c.v. injection of 400 ng of anti-SVG-30 showed a decrease in open arm exploration. In comparison, our lowest tested dose of 500 ng had no significant behavioral effects. Species differences may account for these conflicting results. An anti-SVG-30 dose–response study performed in mice may provide insight into the behavioral differences obtained from studies conducted between the two species. An issue underlying the interpretation of the present results is whether the anxiolytic-like effects produced by anti-SVG-30 are due entirely to antagonism of CRF2 receptors. The initially reported Kd of anti-SVG-30 at CRF2β and CRF1 receptors was 1.4 and 153.6 nM, respectively [43]. This demonstrated binding to the CRF1 receptor opens the possibility that microgram doses of anti-SVG-30 also antagonized CRF1 receptors which may have promoted an anxiolytic-like behavioral profile [18], [31], [35], [45]. However, a recent study using a different binding protocol reported that anti-SVG-30 shows an even greater selectivity (1000–10,000-fold) towards vertebrate CRF2 receptors [20], suggesting a lack of interaction between the CRF1 receptor and anti-SVG-30. It is notable that administration of a CRF2 antisense oligonucleotide, which produced ∼70% suppression of CRF2 receptors in the rat’s lateral septum, was highly effective in attenuating conditioned freezing [21]. This result suggests that disrupting the actions of CRF2 receptors may be sufficient to produce a reduction in anxiety behavior.