Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
J Psychopharmacol. 2020 Jan;34(1):137-144. doi: 10.1177/0269881119885917. Epub 2019 Nov 7.
Adenosine A receptors form a mutually inhibitory heteromeric complex with dopamine D receptors such that each receptor exhibits lower sensitivity to its agonist after the opposing receptor agonist is bound. This study analyzed the effects of CGS 21680, an adenosine A agonist, on nicotine conditioned place preference (CPP) in adolescence using a rodent model of schizophrenia (SZ).
Rats were treated from postnatal day (P) 1 to P21 with saline or the dopamine D/D agonist quinpirole (NQ treatment) and raised to P41. After an initial preference test, rats were conditioned with saline or nicotine (0.6 mg/kg base) from P43 to P51. CGS 21680 (0.03 or 0.09 mg/kg) was given 15 minutes before nicotine was administered. The post-conditioning test was administered on P52. On P53, the nucleus accumbens (NAcc) was analyzed for brain-derived neurotrophic factor (BDNF) and glial cell-lined neurotrophic factor (GDNF).
Results revealed that NQ treatment enhanced nicotine CPP, and both doses of CGS 21680 alleviated this enhancement. Nicotine also resulted in a CPP in controls, which was alleviated by both doses of CGS 21680. BDNF closely followed the behavioral results: CGS 21680 alleviated the enhancement in NAcc BDNF in NQ-treated animals, and eliminated the increase in NAcc BDNF produced by nicotine in controls. NQ-treated animals conditioned to nicotine resulted in an increase of NAcc GDNF, but this was eliminated by CGS 21680. Both BDNF and GDNF correlated with CPP performance.
Results revealed that an adenosine A agonist decreased the rewarding aspects of nicotine and its accompanying neural plasticity changes in a model of SZ.
腺苷 A 受体与多巴胺 D 受体形成相互抑制的异源二聚体复合物，使得每种受体在结合其拮抗剂后对激动剂的敏感性降低。本研究采用精神分裂症（SZ）啮齿动物模型分析了腺苷 A 激动剂 CGS 21680 对青春期尼古丁条件性位置偏爱（CPP）的影响。
从出生后第 1 天（P）到 P21 天，用生理盐水或多巴胺 D/D 激动剂喹吡罗（NQ 处理）处理大鼠，并饲养至 P41 天。在初次偏好测试后，从 P43 天到 P51 天，大鼠接受生理盐水或尼古丁（0.6 mg/kg 碱）处理。在给予尼古丁前 15 分钟给予 CGS 21680（0.03 或 0.09 mg/kg）。在 P52 天进行条件后测试。在 P53 天，分析伏隔核（NAcc）中的脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）。
结果表明，NQ 处理增强了尼古丁 CPP，而 CGS 21680 的两种剂量均减轻了这种增强作用。尼古丁也在对照组中产生 CPP，CGS 21680 的两种剂量均可减轻这种 CPP。BDNF 与行为结果密切相关：CGS 21680 减轻了 NQ 处理动物 NAcc BDNF 的增强，消除了对照组中尼古丁引起的 NAcc BDNF 增加。NQ 处理的尼古丁条件动物导致 NAcc GDNF 增加，但这被 CGS 21680 消除。BDNF 和 GDNF 均与 CPP 表现相关。
结果表明，腺苷 A 激动剂降低了 SZ 模型中尼古丁的奖赏作用及其伴随的神经可塑性变化。
