Caffeine, the stimulant in coffee, has been called“the most widely used psychoactive subst

Caffeine, the stimulant in coffee, has been called

“the most widely used psychoactive substance on Earth .”

Synder, Daly and Bruns have recently proposed that

caffeine affects behavior. by countering the activity in

(5) 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.

(10) 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 propose that caffeine, which is struc-

(15) turally 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 attri-

(20) buted to its inhibition of the production of phosphodi-

esterase, an enzyme that breaks down the chemical

called cyclic AMP.A number of neurotransmitters exert

their effects by first increasing cyclic AMP concentra-

tions in target neurons. Therefore, prolonged periods at

(25) the elevated concentrations, as might be brought about

by a phosphodiesterase inhibitor, could lead to a greater

amount of neuron firing and, consequently, to behav-

ioral stimulation. But Snyder et al point out that the

caffeine concentrations needed to inhibit the production

(30) of phosphodiesterase in the brain are much higher than

those that produce stimulation. Moreover, other com-

pounds that block phosphodiesterase’s activity are not

stimulants.

To buttress their case that caffeine acts instead by pre-

(35) venting 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

(40) 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 locomo-

tion.” Theophylline, a close structural relative of caffeine

and the major stimulant in tea, was one of the most

(45) 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-isobuty1-1-methylxanthine(IBMX), which bound very

(50) well but actually depressed mouse locomotion. Snyder

et al suggest that this is not a major stumbling block 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

(55) known only for its stimulatory effects, displays this

property, depressing mouse locomotion at very low

concentrations and stimulating it at higher ones.

The primary purpose of the passage is to______

A．discuss a plan for investigation of a phenomenon that is not yet fully understood

B．present two explanations of a phenomenon and reconcile the differences between them

C．summarize two theories and suggest a third theory that overcomes the problems encountered in the first two

D．describe an alternative hypothesis and provide evidence and arguments that support it

E．challenge the validity of a theory by exposing the inconsistencies and contradictions in it