Zheng H, Rinaman LM (2010) Anxiety-like behavior in the elevated plus maze (EPMZ) depends on noradrenergic (NA) inputs to the anterolateral bed nucleus of the stria terminalis (alBST) in rats. Neuroscience 2010 Abstracts 90.7/FFF13. Society for Neuroscience, San Diego, CA.
Summary: The a2 adrenoceptor antagonist yohimbine (YO) increases transmitter release from NA neurons, activates the HPA stress axis, and increases anxiety-like behavior in rats. YO-induced HPA axis activation depends on collateralized projections from caudal brainstem NA neurons that innervate both the alBST and the medial parvocellular paraventricular nucleus of the hypothalamus (mpPVN) [Banihashemi & Rinaman, J. Neurosci., 2006]. The current study examined whether the same NA projections underlie the anxiogenic behavioral effects of YO. Adult male Sprague-Dawley rats were tested for baseline anxiety-like behavior in the EPMZ. Subsequently, anesthetized rats received bilateral microinjections of saporin toxin conjugated to an antibody against dopamine beta hydroxylase (DSAP) into the alBST to remove sources of NA input; sham control rats were similarly microinjected with vehicle. Two weeks after surgery, rats were re-tested in the EPMZ on three different days, with the first test conducted 30 min after i.p. YO (1.0 mg/kg BW), the second test conducted 30 min after i.p. saline, and the final test conducted without injection. As expected, the number of “anxiogenic” open arm entries was significantly reduced in sham control rats after YO compared to pre-surgery baseline behavior (P<0.01). Conversely, open arm entries were unaffected by YO in DSAP rats, and the YO-induced reduction of time spent in the open arms was significantly attenuated in DSAP rats vs. sham controls (P<0.01). Interestingly, in the final EPMZ test with no i.p. injections, sham control rats but not DSAP rats displayed increased anxiety-like behavior compared to their pre-surgery baseline (sham controls P<0.01; DSAP rats P=0.3). These findings support the view that caudal brainstem NA neurons projecting to the alBST are important for anxious behavior in the EPMZ, consistent with an earlier study utilizing pharmacological blockade of BST NA receptors [Cecchi et al., Neurosci., 2002]. Our ongoing studies are examining whether similar DSAP lesions attenuate conditioned and unconditioned fear and anxiety responses in rats under more ethologically relevant experimental conditions.
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