当前位置： SCI文献检索 > NEUROSCIENCE期刊下所有文献 > Serotonergic potentiation of photic phase shifts: examination of receptor contributions and early biochemical/molecular events.

Serotonergic potentiation of photic phase shifts: examination of receptor contributions and early biochemical/molecular events.

Abstract：

:The 5-HT mixed agonist/antagonist 1-(2-methoxyphenyl)4-[4-(phthalimido)butyl]-piperazine hydrobromide (NAN-190) has been shown to greatly potentiate photic phase shifts in hamsters. The mechanism of this potentiation has yet to be determined. NAN-190 is believed to act primarily through the 5-HT(1A) receptor, but also binds to several other receptors, making it uncertain as to which receptor underlies its potentiation of photic phase shifts. Also uncertain are the intracellular changes in the suprachiasmatic nucleus (SCN) which are associated with such enhanced phase shifting. Here we examine the role of the 5-HT(1A) receptor as well as the physiological underpinnings, in terms of both gene expression and biochemical activation, in the behavioral responses to photic stimuli following pretreatment with NAN-190. Administration of NAN-190 to wildtype mice significantly potentiated late subjective night photic phase shifts, while mice lacking the 5-HT(1A) receptor (knockouts) exhibited an attenuated behavioral response to light when pretreated with NAN-190. In wildtype mice, the protein product of the immediate-early gene c-fos, induced following photic stimulation, was found to be significantly decreased with NAN-190 pretreatment. Similarly, the levels of phosphorylated CREB protein, involved in a biochemical pathway leading to gene transcription, were also attenuated by NAN-190 in the wildtype mice. However, activation of the extracellular signal-regulated kinase I/II (ERK) pathway in wildtype mice, following the light pulse, was not affected by NAN-190 pretreatment, nor was the expression of the circadian clock components Period1 and Period2. These findings suggest that the 5-HT(1A) receptor plays a critical role in the potentiation effect observed with NAN-190, and that NAN-190 may potentiate photic phase shifts at least partly by down-regulating the activity of some (but not all) genes and biochemical pathways involved in coupling the light signal to the output of the circadian clock.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Smith VM,Hagel K,Antle MC

doi

10.1016/j.neuroscience.2009.09.068

subject

Has Abstract

pub_date

2010-01-13 00:00:00

pages

16-27

issue

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(09)01626-1

journal_volume

165

pub_type

杂志文章

在线工具

Serotonergic potentiation of photic phase shifts: examination of receptor contributions and early biochemical/molecular events.