Melatonin reduces motivation for cocaine self-administration and prevents relapse-like behavior in rats

作者：Takahashi Tatiane T; Vengeliene Valentina; Spanagel Rainer^*

来源：Psychopharmacology, 2017, 234(11): 1741-1748.

DOI：10.1007/s00213-017-4576-y

• Addiction
• Psychostimulants
• Clock gene theory
• Progressive ratio
• Reinstatement
• Melatonin receptors

Rationale Melatonin is a hormone involved in the entrainment of circadian rhythms, which appears dysregulated in drug users. Further, it has been demonstrated that melatonin can modulate the reinforcing effects of several drugs of abuse and may therefore play a role in drug addiction.
Objective Here, we investigated whether administration of melatonin reduces relapse-like behavior and the motivation to seek cocaine in rats.
Methods Male Sprague-Dawley rats were submitted to long-term cocaine self-administration training. Thereafter, melatonin effects were assessed on: (1) the motivation to work for cocaine in the break point test, (2) the relapse-like behavior in the cue-induced reinstatement test, (3) the distance traveled in the open field test, and (4) sucrose preference in a two-bottle choice paradigm. Melatonin, 25 or 50 mg/kg, was injected 34 h after the dark phase onset, 30 min prior to each test.
Results Both doses of melatonin decreased the number of active pokes in both break point and cue-induced reinstatement tests, demonstrating that melatonin can reduce the cocaine-seeking behavior and the motivation to work for cocaine. Administration of the higher dose of this hormone, however, significantly reduced the number of inactive pokes during the cue-induced reinstatement test and tended to reduce animals' locomotor activity in the open field test. Sucrose preference was unchanged in both vehicle-and melatonin-treated animal groups.
Conclusions Our data suggest that melatonin administration may lower the risk of relapse triggered by cues in cocaine-experienced animals.

• 出版日期2017-6
• 单位上海市精神卫生中心