Conroy Susan K, Rodd Zachary, Chambers R Andrew
Laboratory for Translational Neuroscience of Dual Diagnosis Disorders, Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, 791 Union Drive Indianapolis, IN 46202, USA.
Pharmacol Biochem Behav. 2007 Feb;86(2):386-94. doi: 10.1016/j.pbb.2006.07.017. Epub 2006 Aug 28.
Substance use disorder comorbidity in schizophrenia may reflect dysfunctional cortical-striatal-limbic circuitry commonly involved in the addiction process and the pathogenesis of schizophrenia. Rats with neonatal ventral hippocampal lesions (NVHL) demonstrate post-adolescent onset of schizophrenia-like symptoms and increased addiction vulnerability in paradigms using cocaine in adulthood. Here, we investigated response profiles of young adult NVHL vs. SHAM rats to ethanol, an addictive drug with many psychopharmacological effects divergent from those of cocaine, in a locomotor sensitization paradigm. Over 15 days of daily injections of saline, low (0.15 g/kg) or high (1.0 g/kg) doses of ethanol, NVHL rats showed stimulatory effects at the low dose compared to saline and high-dose conditions, while SHAM rats showed expected patterns of dose-dependent suppression of locomotor activity. In a challenge session 2 weeks later in which a moderate dose (0.25 g/kg) of ethanol was given to all subjects, NVHL rats with history of prior ethanol exposure showed greater locomotor activity consistent with installment of alcohol-induced sensitization not present in SHAMs. These findings provide further evidence of enhanced short- and long-term responsivity to abused drugs in a neurodevelopmental model of schizophrenia, and may reflect potentiation of common mechanisms of addiction shared between pharmacologically diverse addictive drugs.
精神分裂症中的物质使用障碍共病可能反映了通常参与成瘾过程和精神分裂症发病机制的皮质-纹状体-边缘回路功能失调。新生大鼠腹侧海马损伤（NVHL）模型表现出青春期后出现类似精神分裂症的症状，且成年后在使用可卡因的范式中对成瘾的易感性增加。在此，我们在运动致敏范式中研究了成年初期NVHL大鼠与假手术（SHAM）大鼠对乙醇（一种成瘾性药物，其许多精神药理学作用与可卡因不同）的反应情况。在连续15天每天注射生理盐水、低剂量（0.15 g/kg）或高剂量（1.0 g/kg）乙醇的过程中，与生理盐水和高剂量条件相比，NVHL大鼠在低剂量时表现出兴奋作用，而SHAM大鼠表现出预期的剂量依赖性运动活动抑制模式。在2周后的激发试验中，给所有受试者注射中等剂量（0.25 g/kg）的乙醇，有乙醇暴露史的NVHL大鼠表现出更大的运动活动，这与SHAM大鼠中不存在的酒精诱导致敏的形成一致。这些发现进一步证明了在精神分裂症神经发育模型中对滥用药物的短期和长期反应性增强，并且可能反映了药理学上不同的成瘾性药物之间共有的成瘾共同机制的增强。
