Hitchcott P K, Phillips G D
Department of Psychology, University of York, Heslington, UK.
Psychopharmacology (Berl). 1998 Dec;140(3):300-9. doi: 10.1007/s002130050771.
We have previously obtained evidence that the mesoamygdaloid dopamine projection modulates the acquisition of a conditioned response (CR) elicited by presentation of a conditioned stimulus (CS) predicting the availability of a natural (sucrose) reward. This property was found to be dependent upon D3, but not D1 or D2, dopamine receptor activation. The aim of the present study was to determine whether the mesoamygdaloid dopamine projection is similarly involved in the acquisition of a drug-associated CR. Thus, two groups of rats with guide cannulae aimed at the nucleus accumbens and amygdala were trained using a Pavlovian conditioning procedure in which an initially neutral CS was paired with a computer-controlled, bilateral intraaccumbens infusion of d-amphetamine (the unconditioned stimulus: US). Conditioning sessions were conducted in standard operant chambers, with each session consisting of a single CS-US trial. For one group of rats, CS presentation was positively correlated with the drug US (Paired group), while for the second group CS and US presentations were negatively correlated (Unpaired group). During training, locomotor activity was recorded and was utilised as the measure both of the unconditioned (UR) and conditioned response (CR). A within-subjects design was utilised to investigate the effect of post-session bilateral intraamygdala administration of R(+) 7-OH-DPAT on the development of the drug-associated CR. Hence, both Paired and Unpaired groups were exposed to two different CSs which were presented on alternate sessions. Post-session bilateral intra-amygdala administration of R(+) 7-OH-DPAT (10 nmol) followed sessions in which one CS was presented, while intra-amygdala vehicle followed sessions in which the alternate CS was presented. The development of a CR occurred only in the presence of a CS that had been positively correlated with presentation of the drug US. Post-session, intra-amygdala administration of R(+) 7-OH-DPAT enhanced the acquisition of this CR. However, R(+) 7-OH-DPAT was without effect upon the unconditioned response to intra-accumbens d-amphetamine. Our previous data indicate a comparable effect of R(+) 7-OH-DPAT on conditioning to a CS associated with a non-drug, natural reward. Therefore, taken together, these findings suggest that D3 dopamine receptors within the amygdala modulate specifically the acquisition of Pavlovian conditioned responses, regardless of whether drug or natural rewards constitute the US.
我们之前已获得证据表明，杏仁核中脑多巴胺投射可调节由呈现预测天然（蔗糖）奖励可得性的条件刺激（CS）所引发的条件反应（CR）的习得。已发现这一特性依赖于D3多巴胺受体的激活，而非D1或D2多巴胺受体。本研究的目的是确定杏仁核中脑多巴胺投射是否同样参与与药物相关的CR的习得。因此，对两组植入了指向伏隔核和杏仁核的引导套管的大鼠，采用经典条件反射程序进行训练，其中最初中性的CS与计算机控制的双侧伏隔核内注入右旋苯丙胺（无条件刺激：US）配对。条件反射训练在标准的操作性条件反射箱中进行，每次训练由一次CS-US试验组成。对于一组大鼠，CS呈现与药物US呈正相关（配对组），而对于第二组，CS和US呈现呈负相关（非配对组）。在训练期间，记录运动活动，并将其用作无条件反应（UR）和条件反应（CR）的测量指标。采用被试内设计来研究训练后双侧杏仁核内给予R(+) 7-OH-DPAT对与药物相关的CR发展的影响。因此，配对组和非配对组都暴露于两种不同的CS，它们在交替的训练时段呈现。在呈现一种CS的训练时段后，双侧杏仁核内给予R(+) 7-OH-DPAT（10 nmol），而在呈现另一种CS的训练时段后，杏仁核内给予溶剂对照。只有在与药物US呈现呈正相关的CS存在时，才会出现CR的发展。训练后，杏仁核内给予R(+) 7-OH-DPAT增强了这种CR的习得。然而，R(+) 7-OH-DPAT对伏隔核内右旋苯丙胺的无条件反应没有影响。我们之前的数据表明，R(+) 7-OH-DPAT对与非药物天然奖励相关的CS的条件反射有类似作用。因此，综合来看，这些发现表明杏仁核内的D3多巴胺受体特异性地调节经典条件反应的习得，无论药物还是天然奖励构成US。
