Khaled Maram A T M, Pushparaj Abhiram, Di Ciano Patricia, Diaz Jorge, Le Foll Bernard
1] Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada [2] Pain Medicine Unit, Department of Anaesthesia, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.
Neuropsychopharmacology. 2014 Dec;39(13):3049-58. doi: 10.1038/npp.2014.158. Epub 2014 Jul 7.
Dopamine D3 receptors are implicated in cue-induced relapse to drug seeking. We have previously shown that systemic administration of a selective D3 antagonist reduces cue-induced reinstatement of nicotine seeking in rats. The current study sought to investigate potential neural substrates mediating this effect. The D3 antagonist SB-277011-A (0.01-1 μg/0.5 μl/side) infused into the basolateral amygdala or the lateral habenula, but not the nucleus accumbens, significantly attenuated cue-induced reinstatement of nicotine seeking. Moreover, infusion of SB-277011-A (1 μg/0.5 μl/side) into the basolateral amygdala or lateral habenula had no effect on food self-administration. Together with the finding that systemic SB-277011-A had no effect on extinction responding, this suggests that the effects observed here were on reinstatement and cue seeking, and not due to nonspecific motor activation or contextual-modified residual responding. The further finding of binding of [(125)I]7-OH-PIPAT to D3 receptors in the lateral habenula and in the basolateral amygdala is consistent with an important role of D3 receptors in these areas in nicotine seeking. It was also found that systemic administration of the selective D2 antagonist L741626 decreased cue-induced reinstatement, consistent with a role of D2 and D3 receptors in modulating this behavior. The current study supports an important role for D3 receptors in the basolateral amygdala and lateral habenula in cue-induced reinstatement.
多巴胺D3受体与线索诱导的觅药复吸有关。我们之前已经表明，全身给予选择性D3拮抗剂可减少线索诱导的大鼠尼古丁觅药行为的恢复。本研究旨在探究介导这种效应的潜在神经底物。向基底外侧杏仁核或外侧缰核而非伏隔核注射D3拮抗剂SB - 277011 - A（0.01 - 1μg/0.5μl/侧），可显著减弱线索诱导的尼古丁觅药行为的恢复。此外，向基底外侧杏仁核或外侧缰核注射SB - 277011 - A（1μg/0.5μl/侧）对食物自我给药没有影响。结合全身给予SB - 277011 - A对消退反应无影响这一发现，这表明此处观察到的效应是针对复吸和线索寻求，而非由于非特异性运动激活或情境改变后的残留反应。在外侧缰核和基底外侧杏仁核中发现[(125)I]7 - OH - PIPAT与D3受体结合，这与D3受体在这些区域对尼古丁寻求的重要作用相一致。还发现全身给予选择性D2拮抗剂L741626可减少线索诱导的复吸，这与D2和D3受体在调节这种行为中的作用一致。本研究支持D3受体在基底外侧杏仁核和外侧缰核中对线索诱导的复吸起重要作用。
