[Histydyl-proline diketopiperazine (HPD), a metabolite of thyrotropin-releasing hormone (TRH), improves the ataxic gait in 3-acetylpyridine (3-AP) treated rats].

Histidyl-proline diketopiperazine (HPD) is the active metabolite deriving from thyrotropin-releasing hormone (TRH). However, its regional distribution in the central nervous system is quite different from TRH. Above all, it is to be noted that cerebellum is one of the richest region of HPD. In rat cerebellum, for example, the concentration of HPD is 20 times higher than that of TRH. This indicates the probable action of HPD within cerebellar system. Recently, a fascinating hypothesis has been proposed by Prasad et al that some activities of TRH are based on its conversion to HPD. The purpose of this experiment is to clarify whether the hypothesis may also be appropriate for the action in the cerebellar system. Twenty four Wistar rats treated with 3-acetylpyridin (3-AP) intraperitoneally were used in our experiment. Before 3-AP administration, those rats were conditioned by electric stimulation to run forward. The 3-AP treated rat is established so as to make an ataxic rat along with a selective degeneration of the inferior olive nucleus. Those ataxic rats were divided into 3 groups according to the test drugs, that is, the group of HPD, TRH (5 mumole/kg each), and saline [the same volume (3.6 ml/kg)] control. Eight rats of each group received an intraperitoneal injection once a day from 5th to 9th day after 3-AP treatment. The behavioral tests were carried out at the 5th, 7th, and 9th day after 3-AP treatment. The ataxic gaits were observed every 30 minutes over 4 hours in succession.(ABSTRACT TRUNCATED AT 250 WORDS)