LYSERGIC ACID DIETHYLAMIDE AND SEROTONIN: A COMPARISON OF EFFECTS ON SEROTONERGIC NEURONS AND NEURONS RECEIVING A SEROTONERGIC INPUT

Abstract

Lysergic acid diethylamide (LSD) administered systemically to rats has been shown to reversibly inhibit serotonin (5-HT)-containing neurons of the raphe nuclei (serotonergic neurons). This inhibition could be due to either a direct effect or an indirect action via a postsynaptic neuronal feedback loop. To compare the responsivity of serotonergic neurons and postsynaptic neurons to LSD, raphe neurons and neurons in four areas (ventral lateral geniculate, amygdala, optic tectum and subiculum) with an identified 5-HT input from the midbrain raphe nuclei were tested for their response to microiontophoretically ejected and systemically administered LSD. Compared to the raphe, cells in these postsynaptic areas were relatively insensitive to microiontophoretic LSD. Raphe cells could be totally inihibited by LSD at ejection currents too low to have any effect on the postsynaptic neurons. In contrast, 5-HT was very nearly equipotent in depressing the firing of the presynaptic (raphe) cells and the postsynaptic cells. To determine if LSD has any indirect inhibitory effect upon raphe neurons via a neuronal feedback, LSD was administered to animals with a mesencaphalic-diencephalic transection. In these animals LSD still produced inhibition of raphe cells at doses comparable to those in control animals. It is concluded : 1) raphe neurons are more sensitive to inhibitory effects of LSD than are postsynaptic neurons ( i.e. , neurons receiving an identified 5-HT input): and 2) the inhibitory effect of low doses of LSD on the presynaptic (raphe) cells is caused by a direct inhibitory action rather than an indirect action via a neuronal feedback.