Lack of tolerance to the depression of raphe unit activity by lysergic acid diethylamide

The responsiveness of serotonin-containing midbrain raphe neurones to lysergic acid diethy-lamide (LSD) was examined in rats made tolerant to LSD by its repeated administration. No significant changes in the dose-response relationships between raphe unit activity and LSD administration were observed following chronic administration of low (100 μg/kg per day for 4 consecutive days) or high doses (1000 μg/kg per day for 4 or 7 days) of LSD. Similarly, no significant change was observed when rats were pretreated with LSD (250 μg/kg) every 6 hr for 4 days. In addition, no significant changes in spontaneous raphe unit activity nor duration of LSD-induced depression of unit activity occurred following chronic LSD pretreatment. These data suggest that the dramatic tolerance which develops to LSD on behavioural tests is not mediated by a change in the sensitivity of serotonin-containing neurons to LSD.