CNS effects of somatostatin

Abstract

exerts direct effects upon the central nervous system (CNS). These effects were first demonstrated with the dopa potentiation test. This neuropharmacologic test was used in 197 1 in hypophysectomized mice treated with melanocyte-stimulating hormone-release-inhibiting factor (MIF-I; Pro-Leu-Gly-NH,) for the first demonstration of the CNS effects of any hypothalamic peptide.’ It involved treatment of mice or rats with a monoamine oxidase inhibitor (pargyline), the test substance, and a dose of dopa at the threshold level for behavioral hyperactivity. In this test, somatostatin was found to maximally increase behavioral activity at a lower dose than the well-known tricyclic antidepressants and antianxiety agents, substance P, and angiotensin I.” However, the hypothalamic tripeptides MIF-I’ and thyrotropin-releasing hormone (TRH)” were much more potent than somatostatin, as was the brain pentapeptide methionine-enkephalin4 and the pituitary hormone, cu-melanocyte-stimulating hormone (wMSH).~ Luteinizing hormonereleasing hormone (LHRH) appeared slightly more potent than somatostatin in the dopa potentiation test, particularly in hypophysectomized mice.“,’ Using the dopa potentiation assay in conjunction with several other neuropharmacologic tests, we have been able to show a pattern for somatostatin that is different from those for the other hypothalamic peptides tested. Additional test systems further differentiate the activity patterns of the naturally occurring brain peptides. One of these tests resembles the dopa potentiation system except that serotonin is used in place of dopa. Unlike TRH, but like MIF-I and cu-MSH, somatostatin was inactive in this serotonin potentiation test. Both the dopa and serotonin potentiation assays can be converted into antagonism tests primarily by the use of larger doses of these two biogenic amines; somatostatin, like many other hypothalamic peptides, was inactive in these two antagonism tests.z Another test that has been used to characterize the CNS activity of some of the peptides involves reversal of the tremors induced by oxotremorine. Somatostatin was inactive in this system,’ which is considered by some investigators to be an animal model of Parkinson’s disease; the only hypothalamic peptide known to be effective is MIF-I.X.!’ The ability of peptides to reduce the aggression of mice trained to fight in response to footshock has also revealed differences in their CNS actions. cu-MSH seemed to increase the fighting,” whereas enkephalin reduced it.’ Somatostatin, at a dose of 10 mg/kg body weight, did not cause even the minimal increases found after administration of TRH, MIF-I, and LHRH.’ Similarly, the same dose of so