Acute effects of antisense antagonism of a single peptide neurotransmitter in the circadian clock

The circadian clock that resides in the suprachiasmatic nucleus (SCN) of the hypothalamus is the major neural pacemaker driving most 24-h rhythms in mammals. Several neurotransmitter peptides are synthesized within this nucleus and communicate rhythmically with other cells in the SCN as well as with cells in other regions of the brain. At the present time, little is known about their role in regulating outputs of the clock. We demonstrate that antisense oligodeoxynucleotides corresponding to the NH2-terminus and the translation start site of vasoactive intestinal peptide (VIP) mRNA infused into the suprachiasmatic region of rats temporarily abolishes the circadian rhythm of corticosterone secretion without influencing stress-related corticosterone secretion in the same animals. Levels of VIP peptide are suppressed 30% on the second day after antisense treatment. These results indicate that a single neuropeptide transmitter in the circadian clock may serve a distinct role in the control of specific circadian rhythms.