Effects of long-term administration of phenelzine on reticular-elicited hippocampal rhythmical slow activity

All anxiolytics so far tested show a common reduction in the frequency of reticular-elicited hippocampal rhythmical slow activity (RSA). Acute administration of the tricyclic antidepressant imipramine shares this effect with anxiolytics. The present experiment tested whether the MAO inhibitor antidepressant phenelzine shares this common effect of anxiolytics and imipramine on hippocampal RSA. Rats, implanted with reticular stimulating electrodes and subicular recording electrodes, received four acute doses (0.2, 2.0, 6.0 and 18 mg/kg) or one chronic dose (2 mg/kg/day for 35 days) of phenelzine. Acute administration of phenelzine failed to systematically affect RSA frequency. Chronic injections of phenelzine eventually produced a reduction in RSA frequency combined with a gradual increase in baseline RSA frequency. The absence of immediate action and the production of a chronic reduction in RSA frequency are distinct from the documented effects of anxiolytics and imipramine, whereas the increase in baseline RSA frequency is similar to imipramine. The different influence of phenelzine on RSA frequency compared with anxiolytics (including imipramine) is consistent with the different clinical profiles of these drugs.