Wise R A, Bozarth M A
Department of Psychology, Concordia University, Montreal, P.Q., Canada.
Psychiatr Med. 1985;3(4):445-60.
Drugs of abuse have in common the fact that they serve as biological rewards. They presumably do so because of their ability to activate endogenous brain circuitry. By determining the brain circuitry activated by rewarding drug injections, much can be learned about the degree to which there is a common basis for the abuse liability of seemingly different drugs. The brain circuitry activated by two classes of abused drugs, psychomotor stimulants and opiates, is now partially understood; the current evidence suggests a shared mechanism of stimulant reward and opiate reward. The identified portion of the circuitry involves dopamine-containing cells of the ventral tegmental area and their fiber projections to the cells of the nucleus accumbens. Morphine activates these cells in the region of the cell bodies; it may have direct actions on receptors imbedded in the dopaminergic cell membrane, or it may act on afferent terminals that synapse on the dopaminergic cell bodies or dendrites. Cocaine and amphetamine act at the terminals of the dopaminergic fibers to nucleus accumbens and perhaps other structures. The shared activation of the dopaminergic input to nucleus accumbens accounts for the behaviorally activating and the rewarding effects of both stimulants and opiates (the opiate stimulant action is not widely known because it is usually masked by depressant actions of opiates in other, antagonistic, brain circuits). The activation of dopaminergic systems also accounts for amphetamine euphoria; it almost certainly accounts for cocaine euphoria and it probably accounts for opiate euphoria as well. Opiates and psychomotor stimulants clearly have many other actions which are not shared; nonshared actions must account for the well-known differences in the subjective effects of opiates and stimulants. One of the major nonshared actions is physical dependence. Opiates gain access to a major component of the circuitry mediating opiate physical dependence through opiate receptors in the periaqueductal gray matter. This receptor population is anatomically distinct from the population mediating the rewarding effects of opiates in nondependent animals. While both opiates and stimulants can activate (though by quite different mechanisms and at quite different loci) the dopaminergic circuitry underlying reward phenomena, only opiates activate the separate circuitry underlying dependence phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)
滥用药物的共同特点是它们能带来生物性奖赏。它们可能是因其激活内源性脑回路的能力才如此。通过确定奖赏性药物注射所激活的脑回路，我们可以了解到看似不同的药物在滥用倾向方面有多大程度的共同基础。目前，两类滥用药物（精神运动性兴奋剂和阿片类药物）所激活的脑回路已部分为人所知；目前的证据表明，兴奋剂奖赏和阿片类药物奖赏存在共同机制。已确定的该脑回路部分涉及腹侧被盖区含多巴胺的细胞及其向伏隔核细胞的纤维投射。吗啡在细胞体区域激活这些细胞；它可能直接作用于嵌入多巴胺能细胞膜的受体，也可能作用于与多巴胺能细胞体或树突形成突触的传入终末。可卡因和苯丙胺作用于多巴胺能纤维到伏隔核及其他可能结构的终末。多巴胺能输入到伏隔核的共同激活解释了兴奋剂和阿片类药物在行为上的激活和奖赏作用（阿片类药物的兴奋作用并不广为人知，因为它通常被阿片类药物在其他拮抗脑回路中的抑制作用所掩盖）。多巴胺能系统的激活也可以解释苯丙胺引起的欣快感；几乎可以肯定它能解释可卡因引起的欣快感，可能也能解释阿片类药物引起的欣快感。阿片类药物和精神运动性兴奋剂显然还有许多其他不同的作用；这些不同的作用必定能解释阿片类药物和兴奋剂在主观效应方面的众所周知的差异。其中一个主要的不同作用是身体依赖性。阿片类药物通过中脑导水管周围灰质中的阿片受体进入介导阿片类药物身体依赖性的脑回路的一个主要组成部分。这群受体在解剖学上与介导非依赖性动物中阿片类药物奖赏作用的受体群不同。虽然阿片类药物和兴奋剂都能激活（尽管通过截然不同的机制且在截然不同的位点）奖赏现象背后的多巴胺能脑回路，但只有阿片类药物能激活依赖性现象背后的独立脑回路。（摘要截选至400词）
