Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 363, Issue -, Pages 61-69Publisher
ELSEVIER
DOI: 10.1016/j.bbr.2019.01.035
Keywords
Cocaine; Clock gene; Circadian rhythm; Drug dependence
Categories
Funding
- Natural Science Foundation of China [81171251, 81871071]
- Beijing Natural Science Foundation [7162101]
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Drug addiction is a widespread social problem, which not only brings adverse consequences to the human body, but also causes great burden to the society. However, it's still unclear how the long-term and sustained cocaine exposure will affect clock genes' expression in the reward related brain areas. We hypothesize that chronic cocaine exposure causes changes in the circadian rhythmic expression of clock genes in brain regions associated with reward, since previous studies have shown that cocaine use causes circadian disorders. Sprague-Dawley male rats were administrated with cocaine 20 mg/kg at ZT4 through intraperitoneal injection for 21 consecutive days. Twenty-four hours after the last cocaine administration brain samples were collected at 4-h intervals for 24 h (every 4h: ZT 0; ZT 4; ZT 8; ZT 12; ZT 16; ZT 20) to examine expression of rPerl, rPer2, rPer3, rCry, rBmal1 and rClock by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR). We found that chronic cocaine exposure to rats resulted in significantly disturbances in expression of clock genes in reward related brain areas compared to saline - treated rats. In cocaine-treated rats, rPerl expression in the suprachiasmatic nucleus (SCN), prefrontal cortex (PFC) and ventral tegmental area (VTA); rPer2 expression in the nucleus accumbens (NAc) shell and hippocampus; rPer3 expression in the NAc core; rCry expression in the SCN and PFC; rBmall expression in the SCN and NAc core showed robust circadian rhythms that were essentially identical to those in control rats. However, robust circadian rhythm in rPerl expression in the SCN and rCry expression in the PFC was nearly completely phase - reversed in cocaine-treated rats. A blunting of circadian oscillations of rPerl expression occurred in the NAc core and shell and hippocampus; of rPer2 expression occurred in the SCN, PFC, NAc core and hippocampus; of rPer3 expression occurred in the SCN, PFC, NAc shell, hippocampus and VTA; of rCry expression occurred in the NAc core and shell, hippocampus and VTA; of rBmall expression occurred in the PFC, NAc shell, hippocampus and VTA in cocaine - treated rats. These rhythm changes accompanied by significant increase in rPerl, rPer2, rPer3 and rBmall in the PFC, rPerl, rPer2 and rBmall in the hippocampus; significant decrease in rPer2, rPer3 and rCry in the SCN, rPer3, rCry, rBmall and rClock in the NAc core compared to control rats. rClock expression in cocaine - treated rats showed no rhythmic change, identical to control rats.These results suggest that chronic cocaine exposure results in disturbances in clock genes' expression in reward related areas.
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