| dc.description | The neurotransmitter serotonin (5-HT) has been implicated in the regulation of neuronal growth in vitro. Using the relatively simple nervous system of the snail Achatina fulica, an investigation into the role of 5-HT in regulating neuronal outgrowth in situ was undertaken. Following a unilateral crush or cut to the cerebrobuccal connective (CBC) in Achatina, cerebral and buccal neurons were observed to undergo rapid axonal regeneration and profuse neuronal outgrowth (sprouting). These responses were accompanied by the distal degeneration of severed serotonergic fibers from the ipsilateral metacerebral giant cell (MCG) which resulted in a unilateral depletion of 5-HT in the CBC and buccal ganglia during the first week of injury. Two approaches were used to examine the potential role of this depletion of 5-HT in causing some of the sprouting responses that accompany injury. The first involved the use of pharmacological agents known to deplete 5-HT in the intact, unlesioned animal. Twenty-one days following administration of the 5-HT neurotoxin, 5,7-dihydroxytryptamine, or the 5-HT synthesis inhibitor p-chlorophenylalanine, axonal and single cell dye-labeling techniques revealed the aberrant sprouting of central neurons, including the MCG. HPLC/EC measurements confirmed that this sprouting response was accompanied by a significant depletion of 5-HT levels in the CNS. The second approach involved an examination of the necessity of the lesion-induced depletion of 5-HT in causing the neuronal sprouting responses. An exogenous supply of 5-HT was administered by repeated injection to lesioned animals during the 3-4 week recovery period in an attempt to block sprouting responses. Sprouting responses among some but not all, cerebral and buccal neurons were found to be significantly attentuated as assessed by axonal dye-labeling techniques. Sprouting by the contralateral MCG (cMCG), was also found to be significantly diminished by repeated 5-HT injections. Control injections of 5-hydroxytryptophan or dopamine, however, were without effect. Furthermore, the inhibition of cMCG sprouting by 5-HT could be antagonized by the prior administration of the vertebrate 5-HT$\sb2$ receptor blocker, cyproheptadine (CYP), but not other 5-HT$\sb2$, 5HT$\sb1$ or 5HT$\sb3$ receptor blockers. In order to examine a possible direct action upon the MCG, 5-HT was applied focally to the MCG soma in vitro. Electrophysiological recordings showed that the MCG responds to 5-HT application with a slow depolarizing response which was also blocked by CYP. These results support the in vitro evidence for a depolarization-induced inhibition of neuronal growth and provide evidence that 5-HT operates in situ within the CNS to control neuritic projections. | en_US |
