Long-term narcotic exposure reduces caudate cyclic nucleotide levels, protein phosphorylation and tyrosine hydroxylase activities.

Chronic morphine implantation was repeated at three-day intervals with increasing doses of morphine base. Caudate tissues from brains of these animals evidenced significantly lower levels of 3', 5'-AMP and lower activities of endogenous protein phosphorylation and tyrosine hydroxylase $\text{in}$$\text{vitro}$. 3', 5'-GMP levels were no longer altered from control levels. The effects of the three week incrementing morphine dose treatment were still evident in the biochemical measures of caudate tissues from brains of animals withdrawn and abstinent for three successive weeks.