Increased brain histamine H sub(3 )receptor expression during hibernation in golden-mantled ground squirrels

Hibernation is a state of extremely reduced physiological functions and a deep depression of CNS activity. We have previously shown that the histamine levels increase in the brain during hibernation, as does the ratio between histamine and its first metabolite, suggesting increased histamine turnover during this state. The inhibitory histamine H sub(3 )receptor has both auto- and heteroreceptor function, rendering it the most likely histamine receptor to be involved in regulating the activity of histamine as well as other neurotransmitters during hibernation. In view of accumulating evidence that there is a global depression of transcription and translation during hibernation, of all but a few proteins that are important for this physiological condition, we reasoned that an increase in histamine H sub(3 )receptor expression would clearly indicate an important hibernation-related function for the receptor. In this study we show, using in situ hybridization, that histamine H sub(3 )receptor mRNA increases in the cortex, caudate nucleus and putamen during hibernation, an increase that is accompanied by elevated receptor binding in the cerebral cortex, globus pallidus and substantia nigra. These results indicate that there is a hibernation-related increase in H sub(3 )receptor expression in cortical neurons and in striatopallidal and striatonigral GABAergic neurons. GTP--S binding autoradiography shows that the H sub(3 )receptors in the globus pallidus and substantia nigra can be stimulated by histamine throughout the hibernation cycle, suggesting that they are functionally active during hibernation. These results show that the histamine H sub(3 )receptor gene is one of the few with a transcript that increases during hibernation, indicating an important role for the receptor in regulating this state. Moreover, the receptor is functionally active in the basal ganglia, suggesting a function for it in regulating e.g. dopaminergic transmission during hibernation.