The effect of serotonin depletion on the discriminability of LSD

Nine groups of rats were trained to discriminate LSD (0.12 mg/kg) from saline in a two-lever, water-reinforced, drug discrimination procedure. After stable discriminative performance was obtained (>95% correct), groups were administered one of several treatments which lower the concentration of serotonin (5-HT) in brain: (1) 12.5, 25, 50, 100 or 200 microgram of 5,7-dihydroxytryptamine (5,7-DHT) intraventricularly (IVT); (2) 3 X 100 mg/kg of p-chlorophenylalanine (PCPA) intraperitoneally (IP); or (3) 20 mg/kg of p-chloroamphetamine (PCA) IP. Control rats received either IVT injections of 5,7-DHT vehicle or IP injections of PCA or PCPA vehicles. Beginning 12 days after treatment, lever preference following various doses of LSD was determined. The results indicated that only the 200 microgram dose of 5,7-DHT and PCPA caused a significant potentiation of LSD-lever responding at the 0.03 mg/kg dose of LSD while all treatments except 12.5 and 25 microgram of 5,7-DHT resulted in significant depletion of 5-HT. Moreover, amount of 5-HT and percent LSD responding following 0.03 mg/kg LSD were not significantly correlated. It was concluded that 5-HT depletion, per se, cannot account for supersensitivity to the behavioral effects of LSD.