Studies on the specificity of neurochemical and behavioral effects of LSD-25

Brain perfusion experiments of conscious rats engaged in operant behavior and administered fluoxetine or LSD, with or without prior injection of 5-HTP, indicate there is probably more than one functional pool of 5-HT in the CNS. Furthermore, the fact that prior loading with the precursor is necessary before unmasking an effect of LSD suggests the LSD-sensitive pool is newly synthesized and represents only a small fraction of total CNS serotonin. Separating the effects of LSD's behavioral action into pausing (disruption) and depressed responding rate, with or without pausing, enabled us to demonstrate blockade of the disruption by methysergide without blockade of the decreased responding rate. Mianserin blocks both effects of LSD's action. We suggest that behavioral effects of low doses of LSD are due to sympathetic arousal and may offer a model for agitated depression and/or anxiety and that drugs of the mianserin-type may prove useful for treating some forms of anxiety, as well as depression.