Prevention of inhibitory effect of dorsal raphe nucleus lesions on ovulation and LH surge by 5-HT 2A/2C receptor agonists in female rats

Abstract

In order to investigate the role of the dorsal raphe nucleus and the serotonergic system in the regulation of ovulation, the number of ova and plasma luteinizing hormone (LH) concentrations were measured in female rats after making lesions in this nucleus (DRL) and/or treatment with 5-hydroxytryptamine (5-HT) receptor agonists or antagonists. DRL or sham lesion was made on the afternoon of proestrous (12:00-14:00 h) under ether anesthesia and the number of ova in the oviduct was counted on the next estrous and diestrous morning. In some animals, blood samples were taken via the atrial cannula during the proestrous evening for the radioimmunoassay of LH. All intact control and sham-operated females ovulated and plasma LH increased between 19:00 and 21:00 h. In contrast, ovulation was seen in only 36% of DRL rats. LH surge did not occur in this group. However, 80% of DRL rats ovulated after treatment with (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride [(+/-)-DOI; a 5-HT 2A/2C receptor agonist] at 15:00 h on proestrous day. LH surge was also observed in the DRL rats with (+/-)-DOI. On the other hand, only 8% of DRL rats ovulated after treatment with buspirone (5-HT 1A receptor agonist). Furthermore, when mianserin (5-HT 2A/2C receptor antagonist) was administered at 16:00 h on proestrous day, ovulation was not seen in all rats without DRL. These results suggest that the dorsal raphe nucleus plays an important role in induction of LH surge and ovulation and the 5-HT 2A/2C receptor system is involved in this mechanism.