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Central Nociceptin/Orphanin (N/OFQ) increases inducible cAMP element repressor (ICER) expression in the rat forebrain

Intracerebroventricular (ICV) and peripheral administration of the opioid like peptide, N/OFQ, in conscious rats produces diuresis and antinatriuresis in addition to marked effects on cardiovascular function and decreases in renal sympathetic nerve activity. Because N/OFQ produces its neuronal inhibitory effects in part via the inhibition of cyclic AMP, it may also change the expression of endogenous transcriptions factors involved in suppression of cyclic AMP (i.e., ICER). The present study examines N/OFQ‐mediated changes in ICER staining in several CNS regions involved in fluid and electrolyte balance. Urine samples were collected during control (15‐min) and after ICV vehicle (V, n=8) or N/OFQ (10 μg; n= 8). 3 additional urine samples (15‐min) were collected after the ICV injection. The forebrain was processed for ICER using polyclonal anti‐ICER antibody raised in rabbit. In VEH injected rats, renal excretion of water or sodium was not altered. N/OFQ produced a rapid and marked increase in urine flow and decrease in urinary sodium excretion rate. In addition, ICV N/OFQ produced significant increases in ICER staining in the supraoptic nucleus (VEH, 15 ± 8; N/OFQ 40 ± 9; P < .05), median preoptic nucleus (VEH, 19 ± 7; N/OFQ 40 ± 9; P < .05), organum vasculosum of the lamina terminalis (VEH, 31 ± 8; N/OFQ 114 ± 42; P < .05), medial preoptic area (VEH, 33 ± 15; N/OFQ 93 ± 33; P < .05), and central nucleus of the amygdala (VEH, 15 ± 13; N/OFQ 46 ± 13; P < .05). Together, central ORL‐1 receptor responses in these forebrain regions may contribute directly or indirectly in the diuretic and antinatriuretic effects of N/OFQ.