AN ELECTROGRAPHIC STUDY OF d-LYSERGIC ACID DIETHYLAMIDE AND NINE CONGENERS

¹ Thudichum Psychiatric Research Laboratory, Galesburg State Research hospital, Galesburg, Illinois

Ninety-six rabbits were used for an electrographic analysis of d-lysergic acid diethylamide (LSD) and 9 congeners. Experiments performed on the groups of intact animals showed that sustained drug-induced EEG arousal patterns were obtained with LSD, d-lysergic acidmonoethylamide (LAE), d-lysergic acid morpholide (LSM), d-1-methyl-lysergic acid diethylamide (MLD) and d-lysergic acid dimethylamide (DAM), but not with 1-methyl-3-lysergic acid butanolamide (UML), d-isolysergic acid diethylamide (d-iso-LSD), l-lysergic acid diethylamide (l-LSD) and 2-brom-d-lysergic acid diethylamide (BOL). All drugs which produced EEG activation were psychotomimetic, but the reverse did not necessarily hold true. One hallucinogen, d-lysergic acid amide, failed to elicit EEGarousal. In order to ascertain a site of EEG alerting, a series of transections consisting of sections above the midbrain, below the midbrain and at the level of the first cervical vertebra were made. Cervical transection neither abolished the evoked activation when LSD was given previous to the section nor inhibited the appearance of EEG arousal in rabbits transected prior to the administration of the drug. However, the arousal reaction was abolished by transections caudal to the midbrain, indicating an effective locus for LSD between these planes. Even though LSM, MLD and DAM evoked EEG alerting in animals with intact brain, the drug-induced arousal couldbe neither initiated nor maintained following cervical transection. In contrast, LAE elicited activation following transections posterior to the midbrain whereas sections above the midbrain abolished the drug-induced pattern. These results indicate effective loci for EEG alerting of the hallucinogens in the lower brainstem region. In general, our results show that those psychotomimetic compounds containing the N-diethyl configuration exhibited loci of action in the lowerbrainstem. Furthermore, it has been suggested that the indole group and the N-diethyl or N-dimethyl configuration are important in producing changes in the site of EEG activation as well as in psychotomimetic behavior.