Pharmacologic specificity of antidepressive activity by monoaminergic neural transplants

Previous studies in our laboratory have demonstrated the ability of monoaminergic transplants in the rat frontal cortex to produce antidepressive activity in both the learned helplessness model and the forced swimming 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 activity of monoaminergic transplants. The goal of the present study was to characterize the pharmacologic mechanisms involved in the monoaminergic graft-induced antidepressive activity. Immobility scores in the forced swimming test (FST) were assessed after transplantation of 5-HT-containing 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 significantly reduced immobility scores in the FST in contrast to control transplanted or untreated animals. All groups were assessed pharmacologically with the adrenergic antagonists phentolamine (alpha) and propranolol (beta), and serotonergic antagonists metergoline (5-HT1/5-HT2) and pirenperone (5-HT2). Serotonergic antagonists, particularly the 5HT2 antagonist, blocked the reduction in FST immobility induced by the pineal implants. Adrenergic antagonists not only blocked FST immobility reductions in adrenal medullary grafted animals, but over-compensated for the adrenal transplants, producing a large increase in immobility. The FST reduction induced by pineal and adrenal cografts was blocked by all four monoaminergic antagonists. FST immobility scores in control transplanted and non-transplanted animals were not altered by any of the antagonists. The immobility reduction produced by chronic imipramine treatment was blocked significantly only by propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)