Phelps C E, Mitchell E N, Nutt D J, Marston H M, Robinson E S J
School of Physiology and Pharmacology, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK.
Psychopharmacology (Berl). 2015 Aug;232(15):2697-709. doi: 10.1007/s00213-015-3905-2. Epub 2015 Mar 21.
Successive negative contrast (SNC) describes a change in the behaviour of an animal following a downshift in the quantitative or qualitative value of an expected reward. This behavioural response has been hypothesised to be linked to affective state, with negative states associated with larger and/or prolonged shifts in behaviour.
This study has investigated whether different psychopharmacological treatments have dissociable actions on the SNC effect in rats and related these findings to their actions on different neurotransmitter systems and affective state.
Animals were trained to perform a nose-poke response to obtain a high-value food reward (four pellets). SNC was quantified during devalue sessions in which the reward was reduced to one pellet. Using a within-subject study design, the effects of acute treatment with anxiolytic, anxiogenic, antidepressant and dopaminergic drugs were investigated during both baseline (four pellets) or devalue sessions (one pellet).
The indirect dopamine agonist, amphetamine, attenuated the SNC effect whilst the D1/D2 antagonist, alpha-flupenthixol, potentiated it. The antidepressant citalopram, anxiolytic buspirone and anxiogenic FG7142 had no specific effects on SNC, although FG7142 induced general impairments at higher doses. The α2-adrenoceptor antagonist, yohimbine, increased premature responding but had no specific effect on SNC. Results for the anxiolytic diazepam were mixed with one group showing an attenuation of the SNC effect whilst the other showed no effect.
These data suggest that the SNC effect is mediated, at least in part, by dopamine signalling. The SNC effect may also be attenuated by benzodiazepine anxiolytics.
连续负性对比(SNC)描述了动物在预期奖励的数量或质量价值下降后行为的变化。这种行为反应被假设与情感状态有关,负面状态与行为的更大和/或更长时间的变化相关。
本研究调查了不同的心理药理学治疗对大鼠SNC效应是否具有可分离的作用,并将这些发现与其对不同神经递质系统和情感状态的作用相关联。
训练动物进行鼻触反应以获得高价值的食物奖励(四颗食丸)。在奖励减少到一颗食丸的贬值阶段对SNC进行量化。采用受试者内研究设计,在基线期(四颗食丸)或贬值期(一颗食丸)研究抗焦虑药、致焦虑药、抗抑郁药和多巴胺能药物急性治疗的效果。
间接多巴胺激动剂苯丙胺减弱了SNC效应,而D1/D2拮抗剂氟哌噻吨增强了该效应。抗抑郁药西酞普兰、抗焦虑药丁螺环酮和致焦虑药FG7142对SNC没有特异性作用,尽管FG7142在高剂量时会引起一般性功能损害。α2肾上腺素能受体拮抗剂育亨宾增加了过早反应,但对SNC没有特异性作用。抗焦虑药地西泮的结果不一,一组显示SNC效应减弱,而另一组则无效应。
这些数据表明,SNC效应至少部分由多巴胺信号介导。苯二氮䓬类抗焦虑药也可能减弱SNC效应。