Serotonergic mediation of constant light-potentiated nonphotic phase shifting of the circadian locomotor activity rhythm in Syrian hamsters

1 Department of Biological Sciences, Kent State University, Kent, Ohio; and 2 Department of Anatomy and Neurobiology, University of Kentucky Medical Center, Lexington Kentucky Submitted 19 January 2006 ; accepted in final form 25 February 2006 Short-term (1–3 days) constant light exposure (brief LL) potentiates nonphotic phase shifting induced by sleep deprivation and serotonin (5-HT) agonist stimulation. The present assessments reveal that exposure to brief LL markedly alters the magnitude and shape of the 5-HT 1A,7 receptor agonist, 8-(+)2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahyronapthalene (8-OH-DPAT) phase-response curve, facilitating ( 12 h) phase-advance shifts during the early morning when serotonergics have no phase-shifting effect. Brief LL also reduces the threshold for 8-OH-DPAT shifting at midday, evidenced by 5- to 6-h phase-advance shifts elicited by dosages that have no effect without the LL treatment. The brief LL-potentiated phase advances to intraperitoneal 8-OH-DPAT at zeitgeber time 0 (ZT 0) were blocked by the 5-HT 1A antagonists, pindolol and WAY 100635, indicating that this shifting is mediated by 5-HT 1A receptors. Antagonists with action at 5-HT 7 receptors, including ritanserin and metergoline, were without effect. Although autoradiographic analyses of [ 3 H]8-OH-DPAT binding indicate that brief LL does not upregulate suprachiasmatic nucleus (SCN) 5-HT 1A receptor binding, intra-SCN microinjection of 8-OH-DPAT at ZT 0 in brief LL-exposed hamsters induced shifts similar to those produced by intraperitoneal injection, suggesting that SCN 5-HT 1A receptors mediate potentiated 8-OH-DPAT-induced shifts during the early morning. Lack of shifting by intra-SCN 8-OH-DPAT at ZT 6 or 18 (when intraperitoneal 8-OH-DPAT induces large shifts), further indicates that brief LL-potentiated shifts at these time points are mediated by 5-HT target(s) outside the SCN. Significantly, sleep deprivation-induced phase-advance shifts potentiated by brief LL ( 9 h) at ZT 0 were blocked by pindolol, suggesting that these behavioral shifts could be mediated by the same SCN 5-HT 1A receptor phase-resetting pathway as that activated by 8-OH-DPAT treatment. suprachiasmatic nucleus; sleep deprivation; 8-OH-DPAT Address for reprint requests and other correspondence: J. David Glass, Dept. of Biological Sciences, Kent State Univ., Kent, OH 44242 (e-mail: jglass{at}kent.edu )