Enhanced selective 5-HT depletions in the DHT rat model: denervation supersensitivity and recovery of function

The effects of enhancing 5-HT depletion with multiple intracisternal injections of 5,7-dihydroxytryptamine (DHT) on spontaneous or L-5-hydroxytryptophan (5-HTP)-induced behaviors (videotaped) and locomotor activity (photocell recording) were studied in the adult rat. After four DHT injections, 5-HT content in septum/accumbens, hippocampus, striatum, neocortex, cerebellum, and cervical spinal cord fell to 0-10% of controls. Multiple injections also significantly improved depletions in brainstem and diencephalon, which were not as extensive. Spontaneous locomotor activity (LMA) was increased in DHT-lesioned rats for 1 week. The associated behavioral abnormalities, hindlimb hyperextension and incomplete rearing were also transient and differed from the motor syndrome evoked by 5-HTP. Multiple DHT injections did not qualitatively modify the 5-HTP syndrome but shifted the dose response curve to the left compared to single injections. Syndrome behaviors shared a similar dose threshold and could be evoked with 30 mg/kg 5-HTP. Two weeks after DHT, the locomotor response to 5-HTP (65 mg/kg) was method dependent or biphasic: decreased in brief recordings when syndrome abnormalities were greatest and increased in hour-long recordings. LMA correlated with rearing in controls and inversely with total behavioral abnormality in DHT-lesioned rats injected with 5-HTP. Multiple regression of LMA with regional 5-HT content was significant for hippocampus, striatum, and septum/accumbens. These data suggest that the development of denervation supersensitivity, the proposed mechanism of the 5-HTP-evoked motor syndrome, may be responsible for the rapid recovery of function in LMA.(ABSTRACT TRUNCATED AT 250 WORDS)