Alpha 2-noradrenergic modulation of hippocampal theta activity

The purpose of the present study was to determine the role of norepinephrine in the generation of hippocampal theta activity. Experiments were performed on urethane-anesthetized rats, implanted with recording electrodes in the dentate gyrus and stimulating electrodes in the dorso-medial posterior hypothalamus. The effects of norepinephrine on hippocampal theta activity was studied by directly infusing norepinephrine and other noradrenergic agents into the hippocampus. Norepinephrine microinfusion produced a decrease in the amplitude of theta activity as observed in the polygraph chart record. Subsequent spectral analyses demonstrated a decrease in power at peak theta frequencies, as well as a decrease in power at frequencies between 20-25 Hz (noise). The inhibitory effect of norepinephrine on hippocampal type 2 theta activity was found to be mediated by alpha 2-adrenergic receptors. Microinfusions of an alpha 2 agonist (detomidine) mimicked the effects produced by norepinephrine, whereas alpha 1 and beta agonists were ineffective. The inhibitory effect of detomidine was blocked by microinfusions of an alpha 2 antagonist (tolazoline), which indicates that the site of action was specific to the noradrenergic alpha 2 receptor.