Jenck F, Broekkamp C L, Van Delft A M
CNS Pharmacology Department, Organon International, The Netherlands.
Psychopharmacology (Berl). 1990;100(3):372-6. doi: 10.1007/BF02244609.
The functional role of brain 5-HT and 5-HT receptor subtypes in periaqueductal gray (PAG) induced aversion has been investigated in rats. Antiaversive effects were found with the serotonin agonists TFMPP, mCPP and DOI but not with RU 24969 which was found to facilitate PAG aversion. The first three serotonin agonists share potent 5-HT1C activity while RU 24969 differs with a high 5-HT1A activity. Proaversive effects were found with the mixed 5-HT1C/5-HT2 antagonists cyproheptadine and ritanserin; this effect was already reported for the mixed 5-HT1C/5-HT2 antagonists metergoline and mianserin and is opposite to the effects of the selective 5-HT2 antagonists ketanserin, pirenperone, trazodone and spiperone. The antiaversive effects of mCPP (1 mg/kg) could be prevented by pretreatment of the animals with mianserin (1 and 10 mg/kg). These results suggest that 5-HT1C receptors play an important role in the serotonergic control of PAG aversion. 5-HT1C receptor activation seems to mediate antiaversive effects whereas acute 5-HT1C receptor blockade appears to facilitate PAG aversion. Functional interactions take place between several receptor types in the in vivo control of PAG aversion, where 5-HT1C receptors appear to play a predominant function.
在大鼠中研究了脑5-羟色胺（5-HT）及其受体亚型在导水管周围灰质（PAG）诱导的厌恶反应中的功能作用。发现5-羟色胺激动剂TFMPP、mCPP和DOI具有抗厌恶作用，而RU 24969却没有，反而发现它会促进PAG厌恶反应。前三种5-羟色胺激动剂具有强大的5-HT1C活性，而RU 24969则具有较高的5-HT1A活性。发现5-HT1C/5-HT2混合拮抗剂赛庚啶和利坦色林具有促厌恶作用；这种作用在5-HT1C/5-HT2混合拮抗剂美替拉酮和米安色林中也有报道，且与选择性5-HT2拮抗剂酮色林、哌仑西平、曲唑酮和螺哌隆的作用相反。用米安色林（1和10mg/kg）预处理动物可预防mCPP（1mg/kg）的抗厌恶作用。这些结果表明，5-HT1C受体在5-羟色胺对PAG厌恶反应的控制中起重要作用。5-HT1C受体激活似乎介导抗厌恶作用，而急性阻断5-HT1C受体似乎会促进PAG厌恶反应。在PAG厌恶反应的体内控制中，几种受体类型之间发生功能相互作用，其中5-HT1C受体似乎起主要作用。
