ALPHA2-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.