Abstract
Histidyl-proline diketopiperazine (cyclo (His-Pro)), a cyclic dipeptide derived from thyrotropin-releasing hormone (TRH), is well known as neuromodulator to control food intake, but other functions are unknown. Since cyclo (His-Pro) has been found in wide areas in the central nervous system, this chemical may play roles in other physiological functions. In the present study, we investigated the effects of intraperitoneal (IP) injection of cyclo (His-Pro) at the dose of 0.1mg/kg on various behavioral tests in male Wistar rats. The effects of iontophoretically applied cyclo (His-Pro) on neuron activities in the thalamus and hippocampus were also examined using multibarrel electrodes in urethane anesthetized rats. Cyclo (His-Pro) was injected 15min before each behavioral test. In the open-field test, this chemical increased number of rearing (p <0.05) which indicate facilitating exploratory behavior. In the elevated plus maze test, cyclo (His-Pro) increased the duration of stay in closed arm (p <0.05) suggesting enhanced anxiety. In the passive avoidance test, the cyclic dipeptide reduced the retention time to move to dark compartment where a electrical shock was applied 24 h before indicating suppression of avoidance learning (p <0.05). In the electrophysiological study, cyclo (His-Pro) inhibited neural activities of hippocampal neurons. These findings suggest that the cyclic dipeptide has diverse physiological actions to regulated emotion and learning in the central nervous. [J Physiol Sci. 2007;57 Suppl:S165]
