Carroll Marilyn E, Dougen Ben, Zlebnik Natalie E, Fess Lydia, Smethells John
Department of Psychiatry, University of Minnesota, MMC 392, Minneapolis, MN, 55455, USA.
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, HSF II, Room S216, 20 Penn St, Baltimore, MD, 21201, USA.
Psychopharmacology (Berl). 2022 Dec;239(12):3819-3831. doi: 10.1007/s00213-022-06251-0. Epub 2022 Nov 4.
In a previous study in female rats, voluntary wheel running attenuated incubation of cocaine craving after 30 but not 3 days (Zlebnik and Carroll Zlebnik and Carroll, Psychopharmacology 232:3507-3413, 2015). The present study in male rats, using the same procedure, showed that wheel running reduced incubated craving after both 30 and 3 days of abstinence.
Male rats self-administered i.v. cocaine (0.4 mg/kg) during 6-h sessions for 10 days. They were then moved from the operant chamber to a home cage with an attached running wheel or stationary wheel, for 6 h daily for a 3- or 30-day period when cocaine craving was hypothesized to incubate. Rats were then returned to the operant chamber for a 30-min test of cocaine seeking, or "craving," indicated by responses on the former "drug" lever was formerly associated with drug stimulus lights and responses (vs. no drug stimuli), and lever responding was compared to responses on the "inactive" that was illuminated and counted lever pressing.
Mean wheel revolutions were similar across the 3- and 30-day incubation groups, when both groups of rats were given access to wheel running vs. access to a stationary wheel in controls. Subsequently, when rats were tested in the operant chamber for "relapse" responding (drug-lever responding) on the lever formerly associated with drug access, cocaine craving was reduced by recent running wheel access (vs. stationary wheel access) in both the 3- and 30-day wheel exposure groups.
Voluntary, self-initiated, and self-sustained physical exercise reduced cocaine craving after short- (3 days) and long-term (30 days) abstinence periods in male rats that previously self-administered cocaine. This was contrasted with reduction of cocaine seeking in females after 30-day, but not 3-day, incubation periods under the wheel running vs. stationary wheel conditions in a previous study (Zlebnik and Carroll Zlebnik and Carroll, Psychopharmacology 232:3507-3413, 2015). These initial findings suggest males may be more sensitive to incubated craving for cocaine than females.
在之前一项针对雌性大鼠的研究中,自愿进行轮转运动可在30天后而非3天后减弱可卡因渴求的潜伏期(兹莱布尼克和卡罗尔,《精神药理学》232:3507 - 3413,2015年)。本项针对雄性大鼠的研究采用相同程序,结果显示,在禁欲3天和30天后,轮转运动均能减少渴求的潜伏期。
雄性大鼠在为期10天的6小时时段内静脉注射可卡因(0.4毫克/千克)。然后,将它们从操作箱转移至带有连接转轮或固定轮的饲养笼中,在假定可卡因渴求会潜伏期的3天或30天期间,每天活动6小时。之后,将大鼠放回操作箱进行30分钟的可卡因觅求测试,即“渴求”测试,通过对先前与药物刺激光和反应相关的“药物”杠杆的反应来表示(与无药物刺激相比),并将杠杆反应与对“非活动”杠杆的反应进行比较,后者在有光照时计数按压次数。
在3天和30天潜伏期组中,当两组大鼠都能使用转轮运动而对照组使用固定轮时,平均转轮圈数相似。随后,当在操作箱中对大鼠进行“复吸”反应(药物杠杆反应)测试时,在先前与药物获取相关的杠杆上,近期使用转轮运动的大鼠(与使用固定轮的大鼠相比)在3天和30天转轮暴露组中可卡因渴求均有所降低。
在先前自行注射过可卡因的雄性大鼠中,自愿、自发且自我维持的体育锻炼在短期(3天)和长期(30天)禁欲期后均能减少可卡因渴求。这与先前一项研究(兹莱布尼克和卡罗尔,《精神药理学》232:3507 - 3413,2015年)中在轮转运动与固定轮条件下,雌性大鼠在30天而非3天潜伏期后可卡因觅求减少的情况形成对比。这些初步发现表明,雄性大鼠可能比雌性大鼠对可卡因渴求的潜伏期更敏感。