Psychopharmacologia (Berl.) 37, 67--79 (1974) 9 by Springer-Verlag 1974 Opposed Behavioral Syndromes in Rats with Partial and More Complete Central Serotonergic Lesions Made with 5,6 Dihydroxytryptamine Jaime Diaz, Gaylord Ellison, and David Masuoka Department of Psychology, University of California, Los Angeles and Nettro- pharmacology Research Laboratory, V. A. Hospital, Sepulveda, California Received December 11, 1973 Abstract. Rats with central 5HT lesions made with multiple small injections of 5,6 dihydroxytryptamine (6)<l0 ~g 5,6 DttT) rear more but locomote less than Controls in novel environments, are more reactive to visual stimulation, and con- sume small, frequent meals. A converse behavioral syndrome is observed in rats in which smaller lesions are made (3)<10 ~g 5,6 DHT) and a longer recovery period allowed. These latter animals show increased locomotion and decreased rearing in novel environments, consume large~ infrequent meals, and demonstrate an ex- aggerated responsivity to the analgesic properties of morphine. It is proposed that the behavioral syndrome of rats with partially damaged, supersensitive circuity may clarify some paradoxical aspects of chronic 5tIT disruptions. Key words: 5 HT Lesions -- 5,6 Dihydroxytryptamine -- Exaggerated Recovery and Supersensitivity -- Animal Models -- Chronic Anxiety and Autism. Intracerebral injections of 5,6 dihydroxy~ryptamine (5,6 DHT) have been found to produce central lesions of central serotonin (5HT) axons and terminals (Baumgarten et al., 1971) ; these lesions are most selective- ly confined to 5ttT terminals when small, multiple doses of 5,6 DHT are used (Baumgarten et al., 1973). Following such central 5HT lesions a gradual recovery of 5HT to even greater than normal levels in the hypo- thalamus and brain stem has been reported; paralleling this recovery are observations of sprouting by damaged 5ttT axons (Bjorklund et al., 1973). These compensations and regrowth in damaged 5HT circuitry are similar to changes observed following damage to central norepinephrine (NE) neurons. Central injections of 6-hydroxydopamine (6-0HDA) produce central lesions which are more selectively confined to the ter- minals of •E cells if multiple, small doses of 6-OItDA are used (Sim- monds and Uretsky, 1970). Following such lesioning NE levels in the brainstem and hypothalamus recover, actually developing a greater than normal turnover of the remaining brainstem ~ (Uretsky et al., 1971); sprouting by damaged NE axons has been observed during this post-lesioning period (Katzman et al., 1971). 5*