Modulation of serotonergic projection from dorsal raphe nucleus to basolateral amygdala on sleep-waking cycle of rats.

Putative serotonergic dorsal raphe nucleus (DRN) neurons display a dramatic role in the modulation of behavior. However, it is not clear how this modulation is mediated. The present study investigated the modulatory effects of serotonergic projection of the DRN to the basolateral amygdala (BLA) on the sleep-waking cycle using polysomnograph (PSG) in rats. DRN microinjection of kainic acid (KA) caused insomnia immediately. From the third day, however, slow wave sleep (SWS) and paradoxical sleep (PS) increased markedly. DRN microinjection of p-chlorophenylalanine (PCPA, once a day for 2 days), which inhibits the synthesis of serotonin (5-HT), led to similar effect to KA administration. The percent of sleep-wakefulness began to change on the third day after PCPA microinjection into the DRN, and the effect was most significant on the sixth day. The percent of sleep-wakefulness started to resume on the seventh day. SWS and PS were reduced after excitation of DRN neurons by microinjection of L-glutamate (L-Glu) into the DRN. Preapplication of the nonselective 5-HT receptor antagonist methysergide (MS) into bilateral BLA blocked the effect of DRN microinjection of L-Glu. Furthermore, bilateral BLA microinjection of 5-hydroxytryptophan (5-HTP), the precursor of 5-HT, on the sixth day after microinjection of PCPA into the DRN, could reverse the effect of PCPA microinjection. These results indicate that the modulation of the DRN on sleep is partially mediated by the serotonergic projection of the DRN to the BLA.