Galosi R, Lenard L, Knoche A, Haas H, Huston J P, Schwarting R K
Institute of Physiology and Neurophysiology Research Group of Hungarian Academy of Sciences, Pecs University Medical School, Pecs, Hungary.
Neuropharmacology. 2001 Mar;40(4):624-33. doi: 10.1016/s0028-3908(00)00181-7.
The mesolimbic dopamine system is thought to play a critical role in reward-related processes. A number of studies have shown that lesion or inhibition of histaminergic neurons acting through H1 receptors can potentiate the effects of drug-induced reward (e.g., psychostimulants and opioids) and can enhance the reinforcing effects of electrical stimulation of the brain. Since dopamine transmission in the nucleus accumbens is thought to provide a crucial link in these histaminergic actions, we examined the effects of local histamine application (0.1, 1.0 and 10.0 micromol/l) on dopamine and its metabolites in the nucleus accumbens of anesthetized rats by means of unilateral reverse dialysis. To study the influence of H1 receptors, we also applied the H1-receptor antagonist pyrilamine (10.0 and 20.0 mg/kg, intraperitoneally) 20 min before histamine administration (1 mmol/l). Finally, pyrilamine (0.1, 1.0 and 10.0 micromol/l) was locally administered into the nucleus accumbens. The data show that histamine can enhance extracellular dopamine levels in the nucleus accumbens in a dose-dependent way. This increase was partially antagonized by prior peripheral administration of 10 mg/kg, and was completely blocked by 20 mg/kg, of pyrilamine. Finally, intra-accumbens administration of pyrilamine locally decreased dopamine and increased dihydroxyphenylacetic acid and homovanillic acid levels. These data are discussed with respect to the possible interactions between dopaminergic and histaminergic mechanisms in the mesolimbic system and their relation to mechanisms of reinforcement.
中脑边缘多巴胺系统被认为在与奖赏相关的过程中起关键作用。许多研究表明，通过H1受体起作用的组胺能神经元的损伤或抑制可增强药物诱导的奖赏效应（如精神兴奋剂和阿片类药物），并可增强脑电刺激的强化作用。由于伏隔核中的多巴胺传递被认为是这些组胺能作用的关键环节，我们通过单侧反向透析研究了局部应用组胺（0.1、1.0和10.0微摩尔/升）对麻醉大鼠伏隔核中多巴胺及其代谢产物的影响。为了研究H1受体的影响，我们还在给予组胺（1毫摩尔/升）前20分钟腹腔注射H1受体拮抗剂吡苄明（10.0和20.0毫克/千克）。最后，将吡苄明（0.1、1.0和10.0微摩尔/升）局部注入伏隔核。数据表明，组胺能以剂量依赖的方式提高伏隔核细胞外多巴胺水平。预先腹腔注射10毫克/千克的吡苄明可部分拮抗这种升高，而20毫克/千克则可完全阻断。最后，伏隔核内局部注射吡苄明可降低多巴胺水平，并升高二羟苯乙酸和高香草酸水平。本文就中脑边缘系统中多巴胺能和组胺能机制之间可能的相互作用及其与强化机制的关系进行了讨论。
