Prior Haloperidol, but not Olanzapine, Exposure Augments the Pursuit of Reward Cues: Implications for Substance Abuse in Schizophrenia
Prior Haloperidol, but not Olanzapine, Exposure Augments the Pursuit of Reward Cues: Implications for Substance Abuse in Schizophrenia
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DOI：
10.1093/schbul/sbs077
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发表时间：
2013-05-01
影响因子：
6.6
通讯作者：
Samaha, Anne-Noel
中科院分区：
文献类型：
--
作者：
Bedard, Anne-Marie;Maheux, Jerome;Samaha, Anne-Noel
滥用药物和上瘾在精神分裂症中非常普遍。慢性抗精神病药物治疗可能通过在大脑的多巴胺系统中诱导超敏反应而导致这种共病。多巴胺超敏可以增强奖励线索的激励动机特性，奖励线索有助于药物成瘾的维持和严重程度。我们以前已经证明，持续使用氟哌啶醇(HAL)治疗(通过皮下小泵)的大鼠在接受苯丙胺(AMPH)挑战后，与HAL幼稚的大鼠相比，会发展成多巴胺超敏反应，并更积极地追求奖励线索。非典型抗精神病药物被认为比典型药物不太可能产生多巴胺超敏反应。因此，我们比较了HAL和非典型抗精神病药物奥氮平(OLZ)在寻找奖励线索方面的效果。训练大鼠将一个轻音提示与水联系在一起，然后用HAL或OLZ治疗。在停用抗精神病药物后，我们评估了AMPH诱导的杠杆按压对线索的增强。从HAL撤军，但不是从奥尔兹撤军，增强了这一效果。Hal，而不是Olz，也增强了AMPH诱导的精神运动激活和尾壳核中c-fos基因的表达。因此，之前的HAL，而不是OLZ，在AMPH激发后增强了条件性奖赏，这可能与AMPH增强的行为敏感性和AMPH诱导的尾壳核参与有关。这些发现表明，HAL，而不是像Olz这样的非典型个体，以提高对奖励提示的反应性的方式修改了奖励回路。由于对奖励线索的反应增强可以促进寻求药物的行为，因此应该调查非典型抗精神病药物是否可能是有药物滥用或成瘾风险的精神分裂症患者的优先选择。
Drug abuse and addiction are excessively common in schizophrenia. Chronic antipsychotic treatment might contribute to this comorbidity by inducing supersensitivity within the brain's dopamine system. Dopamine supersensitivity can enhance the incentive motivational properties of reward cues, and reward cues contribute to the maintenance and severity of drug addiction. We have shown previously that rats with-drawn from continuous haloperidol (HAL) treatment (via subcutaneous minipump) develop dopamine supersensitivity and pursue reward cues more vigorously than HAL-naive rats following an amphetamine (AMPH) challenge. Atypical antipsychotic drugs are thought to be less likely than typicals to produce dopamine supersensitivity. Thus, we compared the effects of HAL and the atypical antipsychotic olanzapine (OLZ) on the pursuit of reward cues. Rats were trained to associate a light-tone cue with water then treated with HAL or OLZ. Following antipsychotic withdrawal, we assessed AMPH-induced enhancement of lever pressing for the cue. Withdrawal from HAL, but not from OLZ, enhanced this effect. HAL, but not OLZ, also enhanced AMPH-induced psychomotor activation and c-fos mRNA expression in the caudate-putamen. Thus, prior HAL, but not OLZ, enhanced conditioned reward following an AMPH challenge, and this was potentially linked to enhanced behavioral sensitivity to AMPH and AMPH-induced engagement of the caudate-putamen. These findings suggest that HAL, but not an atypical like OLZ, modifies reward circuitry in ways that increase responsiveness to reward cues. Because enhanced responsiveness to reward cues can promote drug-seeking behavior, it should be investigated whether atypical antipsychotics might be a preferential option in schizophrenic patients at risk for drug abuse or addiction.