Jastrzębska Joanna, Frankowska Małgorzata, Suder Agata, Wydra Karolina, Nowak Ewa, Filip Małgorzata, Przegaliński Edmund
Institute of Pharmacology Polish Academy of Sciences, Department of Drug Addiction Pharmacology, 31-343 Kraków, Smętna 12, Poland.
Institute of Pharmacology Polish Academy of Sciences, Department of Drug Addiction Pharmacology, 31-343 Kraków, Smętna 12, Poland.
Brain Res. 2017 Oct 15;1673:30-41. doi: 10.1016/j.brainres.2017.07.016. Epub 2017 Jul 27.
Depression and substance cocaine abuse are disorders with a high frequency of comorbidity. In the present study, we combined bilateral olfactory bulbectomy (OBX), an animal model of depression, with intravenous cocaine self-administration and extinction/reinstatement in rats to investigate the effects of two antidepressant drugs, escitalopram (ESC) and imipramine (IMI), with the goal of determining whether these drugs altered cocaine-induced reinforcement and seeking behaviors. Acute administration of IMI (2.5-30mg/kg) reduced the cocaine reinforcement in OBX and SHAM rats. Moreover, IMI effectively reduced the cocaine-seeking behavior after the drug acute or repeated administration during extinction training in OBX rats and SHAM-operated controls. By contrast, acutely administered ESC (2.5-20mg/kg) did not alter cocaine reinforcement in OBX rats or SHAM-operated controls. The lack of ESC effects was also demonstrated during reinstatement tests to study drug-seeking behavior after ESC repeated daily treatment during extinction trials. However, acute treatment with ESC dose-dependently decreased the cocaine-seeking behavior and relapse triggered by cocaine priming or drug-associated conditioned cues in both OBX and SHAM rats. These results indicate the cocaine anti-reinforcement and anti-seeking efficacy of the two antidepressant drugs studied here. However, the mechanisms for the IMI and ESC activity should be clarified in further studies.
抑郁症和可卡因滥用是共病频率很高的疾病。在本研究中，我们将双侧嗅球切除术（OBX）（一种抑郁症动物模型）与大鼠静脉注射可卡因自我给药及消退/复吸实验相结合，以研究两种抗抑郁药物艾司西酞普兰（ESC）和丙咪嗪（IMI）的作用，目的是确定这些药物是否会改变可卡因诱导的强化和觅药行为。急性给予IMI（2.5 - 30mg/kg）可降低OBX大鼠和假手术大鼠的可卡因强化作用。此外，在OBX大鼠和假手术对照组的消退训练期间，药物急性或重复给药后，IMI有效降低了可卡因觅药行为。相比之下，急性给予ESC（2.5 - 20mg/kg）并未改变OBX大鼠或假手术对照组的可卡因强化作用。在消退试验期间每日重复给予ESC后进行的复吸试验中，也证明了ESC缺乏效果。然而，急性给予ESC剂量依赖性地降低了OBX大鼠和假手术大鼠中由可卡因激发或与药物相关的条件性线索引发的可卡因觅药行为和复吸。这些结果表明了此处研究的两种抗抑郁药物的可卡因抗强化和抗觅药效果。然而，IMI和ESC活性的机制应在进一步研究中阐明。
