Extended action of MKC‐242, a selective 5‐HT 1A receptor agonist, on light‐induced Per gene expression in the suprachiasmatic nucleus in mice

We reported previously that ( S )‐5‐[3‐[(1,4‐benzodioxan‐2‐ylmethyl)amino]propoxy]‐1,3‐benzodioxole hydrochloride (MKC‐242) (3 mg kg −1 , i.p.), a selective 5‐HT 1A receptor agonist, accelerated the re‐entrainment of hamster wheel‐running rhythms to a new 8 hr delayed or advanced light‐dark cycle, and also potentiated the phase advance of the wheel‐running rhythm produced by light pulses. The molecular mechanism underlying MKC‐242‐induced potentiation of this phase shift, however, has not yet been elucidated. We examined the effects of MKC‐242 on light‐induced mPer1 and mPer2 mRNA expression in the suprachiasmatic nucleus (SCN) of mice. MKC‐242 (5 mg kg −1 , i.p.) potentiated light‐induced mPer1 and mPer2 expression in the SCN of mice housed in constant darkness for 2 days, when mRNA levels were observed 3 hr after light‐exposure. More potentiating action of MKC‐242 on mPer2 expression in the SCN was observed in mice housed in constant darkness for 9–10 days. This facilitatory action of MKC‐242 on mPer1 expression was antagonized by WAY100635, a selective 5‐HT 1A receptor blocker, indicating that MKC‐242 activated 5‐HT 1A receptors. Other drugs such as 8‐hydroxy‐dipropylaminotetralin (10 mg kg −1 , i.p.), paroxetine (10 mg kg −1 , i.p.), buspirone (10 mg kg −1 , i.p.), and diazepam (10 mg kg −1 , i.p.) did not display a potentiating action on light‐induced mPer1 and mPer2 expression in the SCN. In the behavioral experiments, we found that MKC‐242 (5 mg kg −1 , i.p.) potentiated light‐induced phase delays of free‐running rhythm in mice. The present results suggest that prolonged increase of mPer1 or mPer2 expression in the SCN by MKC‐242 may be involved in the potentiation of photic entrainment by MKC‐242 in mice. © 2002 Wiley‐Liss, Inc.