Effect of Cyclic AMP on Morphine Analgesia Tolerance and Physical Dependence

Abstract

ADENOSINE-3′,5′-MONOPHOSPHATE (cAMP) has often been suggested as a second messenger which mediates the action of a variety of hormones¹. The presynaptic location of the cAMP system, and the demonstration of a cAMP dependent protein kinase in mammalian brain tissue, suggest a possible role for cAMP in the central nervous system². It has been suggested, for example, that cAMP may participate in the secretion of acetylcholine³ and the hypophyseal releasing factors in the hypothalamus³. In vitro⁴ and in vivo⁵ studies indicate that some putative neurohormones increase cAMP synthesis by activating adenyl cyclase. The effect of cAMP on brain biogenic amines has also been studied. Shein et al.⁶ showed an increase in serotonin (5-HT) synthesis from tryptophan by cAMP in pineal culture. Tagliamonte et al.⁷ reported that injection of cAMP into the lateral ventricle of rats increases the 5-HT turnover in brain. Results obtained in our laboratory in mice (I. K. H., H. H. L. and E. L. W., unpublished results) indicate that cAMP decreases the endogenous level of cerebral norepinephrine (NE) and dopamine (DA) as well as the conversion of ¹⁴C-tyrosine into ¹⁴C-CA (catecholamines).