Lee K, Kornetsky C
Boston University School of Medicine, Department of Pharmacology, MA 02118, USA.
Pharmacol Biochem Behav. 1998 Jun;60(2):539-44. doi: 10.1016/s0091-3057(98)00020-3.
The effects of fluoxetine on rewarding brain stimulation were determined in eight Wistar rats using a rate-independent discrete-trial threshold measure. Rats were implanted with bipolar, stainless steel electrodes either into the ventral tegmental area (VTA) or medial forebrain bundle (MFB). Acute administration of fluoxetine significantly raised the reward threshold (decreased sensitivity) at doses of 2.5, 5.0, 10.0, and 20.0 mg/kg, i.p., without altering latency of response. There were no significant differences between VTA and MFB groups. To determine the effects of chronic treatment, daily injections of 5.0 mg/kg fluoxetine were administered to rats for 21 days. Chronic treatment of fluoxetine continued to significantly elevate reward thresholds with no evidence of tolerance. The results of these experiments suggest that fluoxetine does not possess abuse potential and that serotonin produces an inhibitory effect on the mesolimbic dopaminergic reward system. Furthermore, these results suggest that the antidepressant effects of fluoxetine are not the direct result of excitation of brain reward systems, at least in the same manner as abused substances, for example, cocaine.
使用与速率无关的离散试验阈值测量方法，在八只Wistar大鼠中确定了氟西汀对脑奖赏性刺激的影响。将双极不锈钢电极植入大鼠的腹侧被盖区（VTA）或内侧前脑束（MFB）。腹腔注射2.5、5.0、10.0和20.0mg/kg剂量的氟西汀进行急性给药，可显著提高奖赏阈值（降低敏感性），且不改变反应潜伏期。VTA组和MFB组之间无显著差异。为了确定慢性治疗的效果，给大鼠每日注射5.0mg/kg氟西汀，持续21天。氟西汀的慢性治疗持续显著提高奖赏阈值，且没有耐受性证据。这些实验结果表明，氟西汀不具有滥用潜力，并且5-羟色胺对中脑边缘多巴胺能奖赏系统产生抑制作用。此外，这些结果表明，氟西汀的抗抑郁作用不是脑奖赏系统兴奋的直接结果，至少与滥用物质（如可卡因）的方式不同。
