Willins D L, Meltzer H Y
Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
Brain Res. 1998 Jan 19;781(1-2):291-9. doi: 10.1016/s0006-8993(97)01267-5.
In vivo microdialysis was used to compare the effects of serotonergic drugs on morphine- and cocaine-induced increases in extracellular dopamine (DA) concentrations in the rat nucleus accumbens (NAc). Systemic administration of the 5-HT2A/2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (2.5 mg/kg, s.c. ) prevented the increase in extracellular DA in the NAc produced by morphine (5 mg/kg, i.p.). In contrast, this dose of DOI had no effect on the ability of cocaine (10 mg/kg, i.p.) to increase extracellular DA concentrations in the NAc. A 5-HT2C selective agonist, 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212, 5 mg/kg, s.c.) also inhibited morphine-induced increases in extracellular DA concentrations in the NAc. Pretreatment of rats with the selective 5-HT2A antagonist, amperozide, had no effect on morphine-induced elevation of NAc DA concentrations. In order to determine if inhibition of the firing of 5-HT neurons contributes to the serotonin agonist-mediated inhibition of morphine-induced accumbens DA release, rats were pretreated with the 5-HT1A agonist, 8-OHDPAT. At a dose of 100 microg/kg (sc), 8-OHDPAT did not interfere with morphine's ability to increase DA concentrations in the NAc. These results suggest that the activation of 5-HT2C receptors selectively inhibits morphine-induced DA release in the NAc in a manner which is independent of the inhibition of 5-HT neurons.
采用体内微透析技术比较了血清素能药物对大鼠伏隔核（NAc）中吗啡和可卡因诱导的细胞外多巴胺（DA）浓度升高的影响。全身给予5-HT2A/2C激动剂1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷（DOI）（2.5mg/kg，皮下注射）可预防吗啡（5mg/kg，腹腔注射）引起的NAc中细胞外DA升高。相比之下，该剂量的DOI对可卡因（10mg/kg，腹腔注射）增加NAc中细胞外DA浓度的能力没有影响。5-HT2C选择性激动剂6-氯-2-[1-哌嗪基]-吡嗪（MK-212，5mg/kg，皮下注射）也抑制了吗啡诱导的NAc中细胞外DA浓度升高。用选择性5-HT2A拮抗剂安哌齐特预处理大鼠对吗啡诱导的NAc中DA浓度升高没有影响。为了确定抑制5-HT神经元放电是否有助于血清素激动剂介导的对吗啡诱导的伏隔核DA释放的抑制作用，用5-HT1A激动剂8-羟基二苯丙氨酸（8-OHDPAT）预处理大鼠。在剂量为100μg/kg（皮下注射）时，8-OHDPAT不干扰吗啡增加NAc中DA浓度的能力。这些结果表明，5-HT2C受体的激活以一种独立于抑制5-HT神经元的方式选择性地抑制吗啡诱导的NAc中DA释放。
