Amohashemi Elahe, Alaei Hojjatallah, Reisi Parham
Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2022 Dec 24;18(1):16-23. doi: 10.4103/1735-5362.363592. eCollection 2023 Feb.
The lateral habenula (LHb), a key area in the regulation of the reward system, exerts a major influence on midbrain neurons. It has been shown that the gamma-aminobutyric acid (GABA)- ergic system plays the main role in morphine dependency. The role of GABA type B receptors (GABAR) in the regulation of LHb neural activity in response to morphine, remains unknown. In this study, the effect of GABAR blockade in response to morphine was assessed on the neuronal activity in the LHb.
The baseline firing rate was recorded for 15 min, then morphine (5 mg/kg; s.c) and phaclofen (0, 0.5, 1, and 2 μg/rat), a GABAR' antagonist, were microinjected into the LHb. Their effects on firing LHb neurons were investigated using an extracellular single-unit recording in male rats.
FINDINGS/RESULTS: The results revealed that morphine decreased neuronal activity, and GABAR blockade alone did not have any effect on the neuronal activity of the LHb. A low dose of the antagonist had no significant effect on neuronal firing rate, while blockade with doses of 1 and 2 μg/rat of the antagonist could significantly prevent the inhibitory effects of morphine on the LHb neuronal activity.
This result indicated that GABAR have a potential modulator effect, in response to morphine in the LHb.
外侧缰核（LHb）是奖赏系统调节中的关键区域，对中脑神经元有重大影响。已有研究表明，γ-氨基丁酸（GABA）能系统在吗啡依赖中起主要作用。GABA B型受体（GABAR）在调节LHb对吗啡反应的神经活动中的作用尚不清楚。在本研究中，评估了GABAR阻断对LHb神经元活动在对吗啡反应中的影响。
记录15分钟的基线放电率，然后将吗啡（5mg/kg；皮下注射）和GABAR拮抗剂法氯芬（0、0.5、1和2μg/大鼠）微量注射到LHb中。使用细胞外单单位记录法研究它们对雄性大鼠LHb神经元放电的影响。
结果显示，吗啡降低了神经元活动，单独阻断GABAR对LHb的神经元活动没有任何影响。低剂量拮抗剂对神经元放电率无显著影响，而1μg/大鼠和2μg/大鼠剂量的拮抗剂阻断可显著阻止吗啡对LHb神经元活动的抑制作用。
该结果表明，GABAR在LHb对吗啡的反应中具有潜在的调节作用。
