Changes in in vivo [(3)H]-Ro15-4513 binding induced by forced swimming in mice

Mice were forced to swim for 5 min in water at a temperature of 12 degrees C (cold water swim stress) or 32 degrees C (warm water swim stress), and stress-induced analgesia (SIA) was measured using the tail-flick test. The cold water swim stress induced non-opioid SIA as well as hypothermia, whereas the warm water swim stress caused opioid SIA. The in vivo binding of [(3)H]-Ro15-4513 was measured in the stressed mice and compared with that in control mice. The specific binding of [(3)H]-Ro15-4513 in the cerebral cortex, hippocampus, and cerebellum was significantly altered by forced swimming in cold water. Apparent association and dissociation rate of [(3)H]-Ro15-4513 binding were decreased, and the change in the dissociation rate was most pronounced in the hippocampus. In contrast, no significant alterations were observed in in vitro binding. The hypothermia induced by the cold water swim stress seems to be the main reason for alterations in the specific binding of [(3)H]-Ro15-4513. The kinetics of a saturable amount of [(3)H]-Ro15-4513 in the blood and brain were also measured. The relative ratio of the radioactivity concentration in the brain to that in the blood was significantly decreased by forced swimming in cold water, indicating that the cold water swim stress induced changes in the nonspecific binding of [(3)H]-Ro15-4513 in the brain. These results together with previous reports suggested that non-opioid SIA induced by the cold water swim stress might be related to alterations in the rates of general ligand-receptor interactions including GABA(A)/benzodiazepine system. Changes in the nonspecific binding might be also involved in non-opioid SIA.