Induction of antidepressive activity by monoaminergic transplants in rat neocortex

To assess the ability of monoaminergic transplants to reduce immobility in the forced swimming test (FST), either adrenal medullary tissue, pineal gland tissue, or equal volumes of sciatic nerve were transplanted into the rat frontal neocortex. In the FST the duration of immobility is thought to indicate the level of antidepressant activity, as immobility times are reliably reduced by antidepressant therapies. Immobility times were reduced in rats with adrenal medullary grafts and pineal grafts to the rat frontal neocortex. In contrast, immobility times were not reduced in control sciatic nerve tissue grafts. Biochemical analysis using HPLC revealed that pineal-grafted neocortex contained higher levels of serotonin (5-HT) and adrenal medullary-grafted neocortex contained higher levels of norepinephrine (NE) than sciatic nerve-grafted or nongrafted controls. Immunocytochemical studies showed that the monoaminergic grafts survived well and continue to produce high levels of monoamines. These results support an important role for neocortical 5-HT and NE transmission in antidepressant activity and suggest that transplants of monoaminergic-containing tissue can reduce biochemical deficits in depression.