P10/63_Q2, 5

Passage 10 (10/63)

Caffeine, the stimulant in coffee, has been called “the most widely used psychoactive substance on Earth.” Snyder, Daly and Bruns have recently proposed that caffeine affect behavior by countering the activity in the human brain of a naturally occurring chemical called adenosine. Adenosine normally depresses neuron firing in many areas of the brain. It apparently does this by inhibiting the release of neurotransmitters, chemicals that carry nerve impulses from one neuron to the next. Like many other agents that affect neuron firing, adenosine must first bind to specific receptors on neuronal membranes. There are at least two classes of these receptors, which have been designated A₁ and A₂. Snyder et al (et al: abbr. (Lat) 以及其他人，等人) propose that caffeine, which is structurally similar to adenosine, is able to bind to both types of receptors, which prevents adenosine from attaching there and allows the neurons to fire more readily than they otherwise would.

For many years, caffeine’s effects have been attributed to its inhibition of the production of phosphodiesterase, an enzyme that breaks down the chemical called cyclic AMP. A number of neurotransmitters exert their effects by first increasing cyclic AMP concentrations in target neurons. Therefore, prolonged periods at the elevated concentrations, as might be brought about by a phosphodiesterase inhibitor, could lead to a greater amount of neuron firing and, consequently, to behavioral stimulation. But Snyder et al point out that the caffeine concentrations needed to inhibit the production of phosphodiesterase in the brain are much higher than those that produce stimulation. Moreover, other compounds that block phosphodiesterase’s activity are not stimulants.

To buttress their case that caffeine acts instead by preventing adenosine binding, Snyder et al compared the stimulatory effects of a series of caffeine derivatives with their ability to dislodge adenosine from its receptors in the brains of mice. “In general,” they reported, “the ability of the compounds to compete at the receptors correlates with their ability to stimulate locomotion in the mouse; i.e., the higher their capacity to bind at the receptors, the higher their ability to stimulate locomotion.” Theophylline, a close structural relative of caffeine and the major stimulant in tea, was one of the most effective compounds in both regards.

There were some apparent exceptions to the general correlation observed between adenosine-receptor binding and stimulation. One of these was a compound called 3-isobutyl-1-methylxanthine (IBMX), which bound very well but actually depressed mouse locomotion. Snyder et al suggests that this is not a major stumbling block (stumbling block: n.障碍物, 绊脚石) to their hypothesis. The problem is that the compound has mixed effects in the brain, a not unusual occurrence with psychoactive drugs. Even caffeine, which is generally known only for its stimulatory effects, displays this property, depressing mouse locomotion at very low concentrations and stimulating it at higher ones.

2.     Which of the following, if true, would most weaken the theory proposed by Snyder et al?

(A) At very low concentrations in the human brain, both caffeine and theophylline tend to have depressive rather than stimulatory effects on human behavior.

(B) The ability of caffeine derivatives at very low concentrations to dislodge adenosine from its receptors in mouse brains correlates well with their ability to stimulate mouse locomotion at these low concentrations.

(C) The concentration of cyclic AMP in target neurons in the human brain that leads to increased neuron firing can be produced by several different phosphodiesterase inhibitors in addition to caffeine.

(D) The concentration of caffeine required to dislodge adenosine from its receptors in the human brain is much greater than the concentration that produces behavioral stimulation in humans.（D）

(E) The concentration of IBMX required to dislodge adenosine from its receptors in mouse brains is much smaller than the concentration that stimulates locomotion in the mouse.

Why the answer is D, can someone explain to me how to figure out this question?

5.     The passage suggests that Snyder et al believe that if the older theory concerning caffeine’s effects were correct, which of the following would have to be the case?

I.      All neurotransmitters would increase the short-term concentration of cyclic AMP in target neurons.

II.     Substances other than caffeine that inhibit the production of phosphodiesterase would be stimulants.

III.   All concentration levels of caffeine that are high enough to produce stimulation would also inhibit the production of phosphodiesterase.

(A) I only

(B) I and II only

(C) I and III only

(D) II and III only（D）

(E) I, II, and III

I chose B, why D is right?

Thanks

题2: 原文: the ability of the compounds to compete at the receptors correlates with their ability to stimulate locomotion in the mouse; i.e., the higher their capacity to bind at the receptors, the higher their ability to stimulate locomotion.实际上就是说The concentration of caffeine required to dislodge adenosine from its receptors in the human brain is (correlates with/as great as/proportioned to) the concentration that produces behavioral stimulation in humans. 而非much greater. 选项D是削弱了be correlate with.

题5: 由于文中Snyder et al认为旧的观点是不对的, 所以Snyder et al point out that the caffeine concentrations needed to inhibit the production of phosphodiesterase in the brain are much higher than those that produce stimulation. Moreover, other compounds that block phosphodiesterase’s activity are not stimulants. 如果这两点都取反的话, 那么旧的观点就是correct的. II和III正是这两点的取反. 所以D正确.