HISTAMINERGIC MODULATION OF NEOCORTICAL SPINDLING AND SLOW-WAVE ACTIVITY IN FREELY BEHAVING RATS

Histaminergic H3 receptor antagonists stimulate neuronal histamine rel ease and could consequently have a number of physiological effects in the brain. The effects of H3 receptor blockade, induced by systemicall y administered thioperamide, were assessed on the frontal cortex elect roencephalographic (EEG) properties in freely behaving rats. The relat ionship of EEG activity variables to endogenous brain histaminergic ma rkers was also examined, both in controls and in portocaval anastomosi s (PCA)operated rats (which show increased levels of brain histamine a nd t-methylhistamine). Thioperamide reduced the incidence of thalamus- regulated EEG spindles, while it slightly increased their amplitude. I t furthermore reduced the spectral power of low-frequency (1.5-5Hz) EE G, which effect was equally distributed over the spindle and non-spind le EEG states. These EEG effects were accompanied by increased motor a ctivity of the animals. Both the low-frequency EEG activity and spindl e incidence correlated inversely with the histamine level of the brain (hypothalamus and cerebellum excluded) while t-methylhistamine level correlated with the degree of thioperamide-induced reduction of slow-w ave EEG activity. The present results provide evidence for the involve ment of endogenous brain histamine level, histamine release (as assess ed by t-methylhistamine level) and H3 receptors in the histaminergic r egulation of neocortical synchronization patterns assumed to be linked to arousal control.