PHARMACOLOGICAL SPECIFICITY OF ANTIDEPRESSIVE ACTIVITY MONOAMINERGIC NEURAL TRANSPLANTS

Previous studies in our laboratory have demonstrated the ability of mo noaminergic transplants in the rat frontal cortex to produce antidepre ssive activity in both the learned helplessness model and the forced s wimming test, as well as to increase monoamine levels in the implanted frontal cortex. These findings implicate increased cortical levels of norepinephrine (NE) and serotonin (5-HT) in the antidepressive activi ty of monoaminergic transplants. The goal of the present study was to characterize the pharmacologic mechanisms involved in the monoaminergi c graft-induced antidepressive activity. Immobility scores in the forc ed swimming test (FST) were assessed after transplantation of 5-HT-con taining pineal gland tissue, NE-containing adrenal medullary tissue, a combination of both tissues, or sciatic nerve (control) into the rat frontal cortex and compared to non-transplanted and chronic imipramine -treated rats. Monoaminergic transplants and imipramine treatment sign ificantly reduced immobility scores in the FST in contrast to control transplanted or untreated animals. All groups were assessed pharmacolo gically with the adrenergic antagonists phentolamine (alpha) and propr anolol (beta), and serotonergic antagonists metergoline (5-HT1/5-HT2) and pirenperone (5-HT2). Serotonergic antagonists, particularly the 5H T(2) antagonist, blocked the reduction in FST immobility induced by th e pineal implants. Adrenergic antagonists not only blocked FST immobil ity reductions in adrenal medullary grafted animals, but overcompensat ed for the adrenal transplants, producing a large increase in immobili ty. The FST reduction induced by pineal and adrenal cografts was block ed by all four monoaminergic antagonists. FST immobility scores in con trol transplanted and non-transplanted animals were not altered by any of the antagonists. The immobility reduction produced by chronic imip ramine treatment was blocked significantly only by propranolol. These results indicate that adrenal medullary and pineal transplants produce sustained antidepressive activity via local interaction with alpha-an d beta-adrenergic receptors or 5HT(2), receptors, respectively, and ma y be mediated by mechanisms distinct from antidepressant drugs.