CIRCADIAN CHANGE OF VIP MESSENGER-RNA IN THE RAT SUPRACHIASMATIC NUCLEUS FOLLOWING P-CHLOROPHENYLALANINE (PCPA) TREATMENT IN CONSTANT DARKNESS

Neuronal activity of the suprachiasmatic nucleus (SCN) is known to be regulated by two major extrinsic factors conveyed by three anatomicall y distinct pathways to the SCN: photic stimulus by the direct retinohy pothalamic tract (RHT) and the indirect geniculohypothalamic tract (GH T), and information from the brainstem by ascending: forebrain seroton ergic (5-hydroxytryptamine: 5-HT) tract. It has been shown that VIP mR NA level in neurons of the SCN is altered by external light, but remai ns stable in constant darkness. In the present study, by using the in situ hybridization technique combined with computer-assisted image ana lysis, we examined VIP mRNA expression in the SCN of rats in which the two major factors were eliminated, i.e. photic stimulus by exposing a nimals in total darkness and 5-HT transmission by three-day successive administration of p-chlorophenylalalnine methylester (an inhibitor of tryptophan hydroxylase, 200 mg/kg, daily). In saline-treated controls , VIP mRNA levels remained almost constant throughout the day. In cont rast, in PCPA-treated rats, a significant rhythm of VIP mRNA was obser ved with a peak at CT 4 and a trough at CT 20. These observations sugg est that the removal of photic and 5-HT influence induces VIP mRNA rhy thm in the SCN, indicating that VIP mRNA is controlled not only by pho tic information but also by the circadian clock.