Association of an odor with activation of olfactory bulb noradrenergic beta-receptors or locus coeruleus stimulation is sufficient to produce learned approach responses to that odor in neonatal rats

Abstract

These experiments examined the sufficiency of pairing an odor with either intrabulbar activation of noradrenergic beta-receptors or pharmacological stimulation of the locus coeruleus to support learned odor preferences in Postnatal Day 6-7 rat pups. The results showed that pups exposed to odor paired with beta-receptor activation limited to the olfactory bulb (isoproterenol, 50 microM) displayed a conditioned approach response on subsequent exposure to that odor. Furthermore, putative stimulation of the locus coeruleus (2 microM idazoxan or 2 mM acetylcholine) paired with odor produced a subsequent preference for that odor. The effects of locus coeruleus stimulation could be blocked by a pretraining injection of the beta-receptor antagonist propranolol (20 mg/kg). Together these results suggest that convergence of odor input with norepinephrine release from the locus coeruleus terminals within the olfactory bulb is sufficient to support olfactory learning.

Figure 1

Pups exposed to odor during intrabulbar infusion of isoproterenol demonstrated a subsequent relative preference (approach) response to that odor. No drugs were infused during the behavioral test that occurred 24 hr after training. Values are means ± SEM. CS = conditioned stimulus, which was citral in this experiment. * p < .05, significantly different from vehicle-infused control pups.

Figure 2

Pups exposed to odor during peri-locus coeruleus infusions of the α-2 antagonist idazoxan demonstrated a subsequent relative preference (approach) response to that odor. No drugs were infused during the behavioral test that occurred 24 hr after training. Values are means ± SEM. CS = conditioned stimulus, which was peppermint in this experiment. * p < .05, significantly different from both vehicle-infused and no-infusion control pups.

Figure 3

Pups exposed to odor during peri-locus coeruleus infusions of acetylcholine (ACh, 2 mM) demonstrated a subsequent relative preference (approach) response to that odor. No drugs were infused during the behavioral test that occurred 24 hr after training. Acquisition of this odor preference could be blocked by a systemic injection of propranolol. Values are means ± SEM. CS = conditioned stimulus, which was citral in this experiment; LC = locus coeruleus. * p < .05, significantly different from both other groups.

Figure 4

Locations of cannula tips (solid circles) in rats used for the experiment shown in Figure 3. The locus coeruleus is depicted in gray and highlighted by the horizontal arrows. Distance from bregma for each coronal section is denoted on the right, as taken from the stereotaxic atlas of Paxinos and Watson (1986).