Dissociations between the effects of LSD on behavior and raphe unit activity in freely moving cats

The hypothesis that the action of hallucinogenic drugs is mediated by a depression of the activity of brain serotonergic (raphe) neurons was tested by examining the behavioral effects of d-lysergic acid diethylamide (LSD) while studying the activity of raphe neurons in freely moving cats. Although the results provide general support for the hypothesis, there were several important dissociations. (i) Low doses of LSD produced only small decreases in raphe unit activity but significant behavoiral changes; (ii) LSD-induced behavioral changes outlasted the depression of raphe unit activity; and (iii) raphe neurons were at least as responsive to LSD during tolerance as they were in the nontolerant condition.