Locus Coeruleus Stimulation Enhances Object Recognition Memory Persistence After Early-Life Stress Independent of Hippocampal Noradrenergic Signaling

BACKGROUND: Early-life stress, such as maternal deprivation (MD), is a stressor that can lead to cognitive deficits in adulthood. Among the neurochemical mechanisms involved in MD-induced pathophysiology are alterations in the dopaminergic and noradrenergic systems. We recently demonstrated that pharmacological stimulation of dopaminergic neurons in the ventral tegmental area (VTA) improves novel object recognition (NOR) memory in rats subjected to MD. Furthermore, projections from the locus coeruleus (LC) to the dorsal hippocampus (DH) are important for memory consolidation. METHODS: From postnatal day (PND) 1-PND10, male and female rats were either subjected to MD or left undisturbed. In adulthood, the animals underwent stereotaxic surgery for bilateral cannulation of the DH and LC. Following recovery and habituation, the animals were trained in the NOR task and immediately received vehicle or timolol in the DH, and either vehicle or NMDA in the LC. NOR memory was assessed at 24 h, as well as 7 and 14 d after training, to evaluate memory consolidation and persistence, respectively. RESULTS: MD impaired NOR memory in male rats, but not in females. Pharmacological stimulation of the LC with NMDA promoted NOR memory persistence in both non-MD and MD males and females. In males, LC stimulation also reversed the MD-associated memory impairment. These effects were maintained despite hippocampal β-adrenergic receptor blockade with timolol. CONCLUSION: These findings suggest that LC-related pathways contribute to the processing of NOR memory persistence following early-life stress in a sex-dependent manner. This effect appears to be independent of hippocampal β-adrenergic signaling.