Differential effects of LSD serotonin and l-tryptophan on visually evoked responses

Alterations in photically-evoked cortical responses were assessed in immobilized artificially respired cats following intraraphe microinjections of LSD and serotonin (5-HT) and IV administration of LSD and l-tryptophan. Both systemic (10-100 micrograms/kg; N = 5) and intraraphe (0.25 microgram; N = 10) LSD significantly increased the amplitudes of the three primary components of the visual evoked response (VER). In contrast, the same VER components were significantly depressed following intraraphe 5-HT (30 micrograms; N = 4) and IV l-tryptophan (100 mg/kg; N = 6), a serotonin precursor that elevates raphe 5-HT levels. Intraraphe cinanserin (180 micrograms; 30 minute pretreatment) completely reversed LSD-induced enhancements in all three components (p less than 0.01). Depressions of VER following intraraphe 5-HT (30 micrograms) were also antagonized by cinanserin, although to lesser degree (p less than 0.05 for first 2 components only) than with LSD. The depressive effects of l-tryptophan (100 mg/kg) were unaffected by cinanserin. Modification of raphe neuronal activity can significantly alter photically evoked responses, and may explain the perceptual disturbances associated with LSD, i.e., depression of an area (raphe) normally inhibiting forebrain areas of the visual system.