Effects of estrogen and progesterone treatment on rat hippocampal NMDA receptors: relationship to Morris water maze performance.

Estrogen modulates NMDA receptors function in the brain. It increases both dendritic spine density and synapse number in the hippocampus, an effect that can be blocked by NMDA antagonist. In this study, we investigated the effect of 17beta-estradiol and progesterone treatment on NMDA receptors in ovariectomized rats. Two different doses were used for 10 weeks. Receptor autoradiography was done on brain sections using [(3)H] MK-801 as a ligand. Our results showed a significant increase in [(3)H] MK-801 binding in the dentate gyrus, CA3 and CA4 areas of the hippocampus of ovariectomized compared to sham operated rats. In addition, we observed similar changes in CA1. 17beta-estradiol treatment in both doses reduced the binding back to the normal level while progesterone treatment did not show any effect. Spatial reference memory was tested on Morris water maze task. Ovariectomy severely impaired spatial reference memory. Estradiol but not progesterone treatment significantly improved the memory performance of the ovariectomized rats. Low dose treatment showed better learning than high dose estrogen treatment. The decrease in the antagonist sites by estradiol treatment could result in an increase in the sensitivity of the hippocampus to the excitatory stimulation by glutamate system and hence the effect of estradiol on learning and memory. The changes of NMDA receptors in the hippocampus support the concept that estrogen-enhancing effect on spatial reference memory could be through the enhancing of NMDA function.

Loss of muscarinic M4 receptors in spinal cord of arthritic rats: implications for a role of M4 receptors in pain response.

Changes in the levels of muscarinic M4 receptors in spinal cord of acute and chronic arthritic rats (animal models of pain) were studied by receptor autoradiography using muscarinic M4 receptor subtype selective ligand. Arthritis was induced in female Lewis rats by single intradermal injection of heat-killed Mycobacterium butyricum and sacrificed 12 days (acute group) and 30 days (chronic and control groups) after induction of arthritis. Our results demonstrate significant reduction in the level of M4 receptors in the spinal cord (Rexed laminae I-X) of acute and chronic arthritic rats compared to controls. These findings suggest that the muscarinic M4 receptor subtype may be involved in cholinergic mechanisms of analgesia.

Distribution of leucine-enkephalin in bone and joint tissues.

The distribution and concentration of leu-enkephalin in periosteum, cortical bone, bone marrow and synovial membrane of normal rats were analysed. Periosteum, cortical bone and bone marrow of the rat femurs were collected as well as the ankles. The distribution of leu-enkephalin was analysed by immunoelectron microscopy and the concentration of leu-enkephalin was measured with radioimmunoassay. Immunoelectron microscopy showed that leu-enkephalin is abundant in monocytes of bone marrow, nerve fibers and endothelial cells in the periosteum and also in macrophage-like-cells of the synovial membrane. The concentration of leu-enkephalin measured by RIA showed highest concentration in bone marrow followed by periosteum and cortical bone. The study supports that leu-enkephalin is present and can be quantified in different compartments of bone and joint tissues suggesting that leu-enkephalin may be involved in the physiological regulation of nociception and immunoregulation.