Affiliation: | * Geriatric Research, Education and Clinical Center Veterans Affairs Medical Center, Seattle, WA 98108, USA † Department of Medicine University of Washington, Seattle, WA 98195, USA ‡ Department of Pharmacology University of Washington, Seattle, WA 98195, USA § Department of Physiology and Biophysics University of Washington, Seattle, WA 98195, USA a Department of Psychology University of Washington, Seattle, WA 98195, USA |
Abstract: | Autoradiographic analysis of 1, 8, 16 and 26-day-old rat brains showed 3H-arginine8-vasopressin (3H-AVP) binding to the cingulate gyrus-dorsal hippocampus (CG) only in the 8-day-old rat brain. Saturation analysis of CG membranes prepared from pups (7–10 days) and adults (90 days) revealed a small but significant increase in binding site concentration in adults compared to pups. However, the Kd of the 3H-AVP binding site increased significantly with age. The Kd of 3H-AVP binding to pup CG membranes was 0.9±0.1 nM, while the adult CG was 5.7±1.0 nM. The pharmacological specificity of 3H-AVP binding sites in the pup and adult CG was similar, but differed markedly from the profile observed in adult septal membranes. The primary specificity difference between the pup CG and septum was the reduced potency of certain V1 receptor antagonists. In competition experiments the CG binding site showed a reduced affinity for the V1 antagonist, [d(CH2)5, Tyr(Me)]AVP. This reduced affinity for the V1 antagonist was also documented autoradiographically using 3H-[d(CH2)5, Tyr(Me)]AVP. The data suggest that the 3H-AVP binding site expressed in the pup CG is not identical to the V1 type receptor present in the periphery and brain of the adult rat. |