Neuroscience Research Laboratory, Dr Panjwani Center for Molecular Medicine & Drug Research (PCMD), International Center for Chemical and Biological Science (ICCBS), University of Karachi, Karachi 75270, Pakistan.
Neuroscience Research Laboratory, Dr Panjwani Center for Molecular Medicine & Drug Research (PCMD), International Center for Chemical and Biological Science (ICCBS), University of Karachi, Karachi 75270, Pakistan.
Pharmacol Biochem Behav. 2018 Jul;170:71-78. doi: 10.1016/j.pbb.2018.05.010. Epub 2018 May 18.
Adaptations within the nucleus accumbens (NAc) and caudate nucleus (CN) dopamine neurotransmission are involved in behavioral sensitization and enhanced incentive motivation towards drug paired stimuli which lead to drug addiction. Serotonin (5-hydroxytryptamine; 5-HT) can modulate dopamine neurotransmission to reduce rewarding effects of drugs of abuse. A recent study from our laboratory shows that rewarding effects of morphine are inhibited in rats co-treated with buspirone. To understand the neurochemical mechanism involved in morphine addiction and its inhibition with buspirone, present study determines the effects of buspirone, morphine and their co-administration on the metabolism of serotonin and dopamine in the NAc and CN. We find that rewarding effects of morphine are associated with an enhancement and attenuation of dopamine metabolism, respectively in the CN and NAc. Serotonin metabolism is enhanced in both regions. Co-administration of buspirone not only prevents rewarding effects of morphine, but its effects on the metabolism of dopamine and serotonin in the NAc and CN are also reversed. Results suggest that 5-HT1A receptor dependent modulation of dopamine neurotransmission in the CN and NAc is involved in the modulation of the rewarding effects of morphine in buspirone co-treated animals. The findings documenting an important role of 5-HT1A receptors in drug addiction suggest that synthetic opioid drugs with agonist activity of 5-HT1A receptors may prove non addictive analgesics.
伏隔核（NAc）和尾状核（CN）多巴胺神经传递的适应性变化参与了行为敏感化和对药物配对刺激的激励动机增强，从而导致药物成瘾。5-羟色胺（5-羟色胺；5-HT）可以调节多巴胺神经传递，减少滥用药物的奖赏作用。我们实验室最近的一项研究表明，在与丁螺环酮共同治疗的大鼠中，吗啡的奖赏作用受到抑制。为了了解吗啡成瘾及其与丁螺环酮抑制的神经化学机制，本研究确定了丁螺环酮、吗啡及其联合给药对 NAc 和 CN 中 5-羟色胺和多巴胺代谢的影响。我们发现，吗啡的奖赏作用与 CN 和 NAc 中多巴胺代谢的增强和衰减分别相关。5-HT 代谢在两个区域都增强。丁螺环酮的联合给药不仅可以防止吗啡的奖赏作用，而且还可以逆转其对 NAc 和 CN 中多巴胺和 5-羟色胺代谢的影响。结果表明，5-HT1A 受体对 CN 和 NAc 中多巴胺神经传递的依赖性调节参与了丁螺环酮共同治疗动物中吗啡奖赏作用的调节。这些发现记录了 5-HT1A 受体在药物成瘾中的重要作用，表明具有 5-HT1A 受体激动活性的合成阿片类药物可能被证明是非成瘾性镇痛药。
