Morissette Marie-Claude, Boye Sandra M
Department of Psychiatry, Université de Montréal and Centre de Recherche Fernand-Seguin, Hôpital Louis-H. Lafontaine, 7331 Hochelaga, Montreal, Quebec, Canada H1N 3V2.
Behav Brain Res. 2008 Feb 11;187(1):17-26. doi: 10.1016/j.bbr.2007.08.021. Epub 2007 Aug 22.
The present experiment used electrolytic lesions in combination with curve-shift scaling to study the functional relation between the habenula and four different brain sites that support operant responding for brain stimulation reward. Rats were implanted with a monopolar stimulation electrode aimed at the lateral hypothalamus, ventral tegmental area, dorsal raphe or median raphe nuclei, and a lesioning electrode in the ipsilateral habenula. Operant nose poking resulted in self-administration of trains of electrical pulses to one of the above stimulation sites. Reward thresholds were derived from response-number curves and defined as the pulse number necessary for half-maximal responding. Rats were tested daily at each of three current intensities that were chosen from individual number-current trade-off functions and that yielded baseline reward thresholds of approximately 10, 20 and 40 pulses/train. Testing resumed 24h after lesioning the habenula (100 muA anodal current, 20-25s) and continued for 3-4 weeks. A total of 19 rats completed the experiment. In five of these, habenular lesions clearly reduced the rewarding effectiveness of the stimulation; reward thresholds increased by approximately 30-245% (0.12-0.54 log10 units). Generally, lesion effects were observed at low and medium current intensities, developed gradually and did not recover. Histological analysis revealed that in two rats the stimulation electrode was located in the posterior lateral hypothalamus, two in the anterior ventral tegmental area and one in the area of the dorsal raphe. These results strongly suggest that the habenula constitutes an important component of the neural circuitry important for brain stimulation reward.
本实验采用电解损伤结合曲线移位标度法,研究缰核与支持脑刺激奖赏操作性反应的四个不同脑区之间的功能关系。给大鼠植入一个单极刺激电极,目标分别为外侧下丘脑、腹侧被盖区、中缝背核或中缝正中核,以及同侧缰核的损伤电极。操作性鼻触导致对上述刺激位点之一自我给予电脉冲串。奖赏阈值从反应次数曲线得出,定义为产生半数最大反应所需的脉冲数。从个体数 - 电流权衡函数中选择三种电流强度,每天对大鼠进行测试,这三种电流强度产生的基线奖赏阈值分别约为10、20和40脉冲/串。在损伤缰核(阳极电流100 μA,20 - 25秒)24小时后恢复测试,并持续3 - 4周。共有19只大鼠完成实验。其中5只大鼠,缰核损伤明显降低了刺激的奖赏效力;奖赏阈值提高了约30 - 245%(0.12 - 0.54 log10单位)。一般来说,在低电流和中等电流强度下观察到损伤效应,效应逐渐发展且未恢复。组织学分析显示,两只大鼠的刺激电极位于下丘脑后外侧,两只位于腹侧被盖区前部,一只位于中缝背核区域。这些结果强烈表明,缰核是对脑刺激奖赏至关重要的神经回路的重要组成部分。