Developmentally-induced hypothyroidism alters the expression of Egr-1 and Arc genes and the sensitivity to cannabinoid agonists in the hippocampus. Possible implications for memory and learning

We analyzed the role of the cannabinoid system in the cognitive deficits caused by developmentally-induced hypothyroidism. We studied in control and hypothyroid rats the effect of a cannabinoid agonist on spatial memory, hippocampal phosphorylation of CREB and expression of early genes. Our results show that, 1-basal hippocampal expression of early genes and spatial learning are decreased in hypothyroid rats; 2-hypothyroid rats are very sensitive to cannabinoid agonists. Low dose of cannabinoid agonist ineffective in controls altered spatial memory, CREB’s phosphorylation and early gene expression in hypothyroids. These effects are not due a change in CB1 receptor (CB1R) content. 3-Treatment of hypothyroid rats with thyroid hormones normalized the biochemical and behavioral responses to cannabinoid agonists but did not correct the low basal levels of early gene transcripts and the deficits in spatial learning. All these data suggest that the hippocampal deregulation of early genes expression could play an important role in the basal cognitive deficits of hypothyroid rats.

► We analyzed the role of cannabinoid system and early genes in the cognitive deficits of hypothyroidism. ► Basal spatial memory and hippocampal expression of Egr-1 and Arc genes are decreased in hypothyroid rats. ► Also the behavioral and the biochemical responses to cannabinoid agonists are altered. ► Treatment with thyroid hormones normalized only cannabinoid agonist’s response, but not basal one. ► Deregulation of Egr-1 and Arc genes may play a role in the cognitive deficits of hypothyroid rats.