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Mood alterations, anxiety, and cognitive impairments associated with adult-onset hypothyroidism often persist despite replacement treatment. In rodent models of hypothyroidism, replacement does not bring 3-iodothyronamine (T₁AM) brain levels back to normal. T₁AM is a thyroid hormone derivative with cognitive effects. Using a pharmacological hypothyroid mouse model, we investigated whether augmenting levothyroxine (L-T₄) with T₁AM improves behavioural correlates of depression, anxiety, and memory and has an effect on hippocampal neurogenesis. Hypothyroid mice showed impaired performance in the novel object recognition test as compared to euthyroid mice (discrimination index (DI): 0.02 ± 0.09 vs. 0.29 ± 0.06; t = 2.515, <i>p</i> = 0.02). L-T₄ and L-T₄+T₁AM rescued memory (DI: 0.27 ± 0.08 and 0.34 ± 0.08, respectively), while T₁AM had no effect (DI: −0.01 ± 0.10). Hypothyroidism reduced the number of neuroprogenitors in hippocampal neurogenic niches by 20%. L-T₄ rescued the number of neuroprogenitors (mean diff = 106.9 ± 21.40, t = 4.99, p_corr = 0.003), while L-T₄+T₁AM produced a 30.61% rebound relative to euthyroid state (mean diff = 141.6 ± 31.91, t = 4.44, p_corr = 0.004). We performed qPCR analysis of 88 genes involved in neurotrophic signalling pathways and found an effect of treatment on the expression of <i>Ngf</i>, <i>Kdr</i>, <i>Kit</i>, <i>L1cam</i>, <i>Ntf3</i>, <i>Mapk3</i>, and <i>Neurog2</i>. Our data confirm that L-T₄ is necessary and sufficient for recovering memory and hippocampal neurogenesis deficits associated with hypothyroidism, while we found no evidence to support the role of non-canonical TH signalling.