Local morphine withdrawal increases c-fos gene, fos protein, and oxytocin gene expression in hypothalamic magnocellular neurosecretory cells

We measured stimulation of c-fos and oxytocin gene expression during excita tion of oxytocin cells induced by systemic or local morphine withdrawal. Fe male rats were made morphine-dependent by intracerebroventricular morphine infusion over 5 d. Morphine withdrawal, induced by systemic injection of th e opioid antagonist naloxone (5 mg/kg) in conscious or anesthetized rats, i ncreased the density of c-fos messenger RNA and of oxytocin heterogeneous n uclear RNA in supraoptic nucleus cells compared with those of nonwithdrawn rats; c-fos messenger RNA was also increased in the magnocellular and parvo cellular paraventricular nuclei of withdrawn rats. Morphine withdrawal incr eased the number of Fos-immunoreactive cells in the supraoptic and magnocel lular paraventricular nuclei of conscious or pentobarbitone-anesthetized ra ts. Morphine withdrawal also increased Fos-immunoreactive cell numbers in t he parvocellular paraventricular nucleus of conscious but not anesthetized rats. Central administration of the alpha(1)-adrenoreceptor antagonist beno xathian (5 mu g/min) did not prevent morphine withdrawal-induced increases in the numbers of Fos-immunoreactive neurons in the supraoptic or magnocell ular paraventricular nucleus. Unilateral microdialysis administration of na loxone (10(-5) M) into the supraoptic nucleus of anesthetized morphine-depe ndent rats increased Fos-immunoreactive cell numbers compared with the cont ralateral nucleus. Finally, we investigated whether dependence could be ind uced by chronic unilateral infusion of morphine into a supraoptic nucleus; systemic naloxone (5 mg/kg) increased Fos-immunoreactive cell numbers in th e morphine-infused nucleus compared with the contralateral nucleus. Thus, m orphine withdrawal excitation increases c-fos and oxytocin gene expression in supraoptic nucleus neurons. This occurs independently from excitation of their ascending noradrenergic inputs, and both dependence and withdrawal c an be induced within the supraoptic nucleus.