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Augmentation of the noradrenergic system in alpha-2 adrenergic receptor deficient mice: anatomical changes associated with enhanced fear memory

2003; Elsevier BV; Volume: 986; Issue: 1-2 Linguagem: Inglês

10.1016/s0006-8993(03)03248-7

1872-6240

M. Frances Davies, Janet Y. Tsui, Judy A. Flannery, Xiangqi Li, Timothy M. DeLorey, Brian B. Hoffman,

Stress Responses and Cortisol

We have investigated sensitivity to the conditioned fear procedure of mice is influenced by the genetic deletion of α2A adrenoceptors (ARs). We observed a heightened freezing response in the discrete cue memory test in α2A AR knockout (α2A AR KO) mice and in D79N mice, a transgenic mouse strain with functionally impaired α2A ARs. No significant differences in contextual memory were observed between control and α2A AR KO or D79N mice suggesting a minimal role for the noradrenergic system in contextual memory. We speculated that the increased freezing response of the α2A AR KO and D79N mice in the discrete cue setting was due to increased release of norepinephrine evoked by the unconditioned footshock stimulus. In α2A AR KO mice we measured a doubling in the number of noradrenergic neurons in the locus coeruleus (LC) and a large increase in the cell volume of tyrosine hydroxylase positive neurons, likely due to selective preservation of large, multipolar neurons in the subcoeruleus. Hyperplasia of the noradrenergic neurons in the nucleus tractus solitarius, A5 and A7, was also observed. α2A AR KO mice exhibit greater c-Fos expression in the LC compared to wild type mice suggesting that the LC neurons in the α2A AR KO mice were spontaneously more active. This study suggests that α2A ARs are involved in the development of the central noradrenergic system and raises the possibility that alterations in α2A AR expression may contribute to variations in fear and stress responses.