Drugs and Behaviour

Drugs that affect the brain are a pretty varied lot. They act on many different types of receptors in the brain. Since these receptors are concentrated in different parts of the brain, and have different functions, you would expect that drugs would be very different in their effects on behaviour.

Some are distinct enough, but it is surprising how many drugs seem to have rather similar effects, acting mainly on arousal levels. They are either sedative or stimulant. The sedative drugs, also known as CNS depressants, include alcohol, the benzodiazepines, anaesthetics, anticholinergics, antihistamines, and many more. These cover at least five different types of receptor (not including the many subtypes). All these drugs make you sleepy, impair attention and memory, slow reaction times,  and impair hand-eye coordination. Other drugs are stimulant, and make you feel more alert, for example caffeine and amphetamines. They tend to improve performance, although this is not always easy to show in people who are wide-awake. 

For those of us who are interested in using drugs to help understand the brain mechanisms underlying behaviour, these similarities are rather frustrating. They led me to propose, (very much tongue in cheek), the volume control hypothesis of drug action (right). The idea is that all these drugs act either by turning the volume up (stimulants) or down (sedatives). 

Obviously this is a sort of "null hypothesis", designed to be overturned. But there is a problem in the literature in that surprisingly few studies have compared different classes of drugs directly with each other. It's very hard to compare drug profiles between studies because it is difficult to be sure that the tests were carried out n the same way, even where standard test batteries were used.

An important part of our research has been building up data on profiles of different drugs, as far as possible using direct comparisons. The first of these studies compared alcohol and temazepam, a benzodiazepine used to help people sleep, and also to combat anxiety and stress. The data showed a clear difference in the effects on psychomotor performance - alcohol led to an increase in errors with no change in speed, while temazepam led to slower reaction times with no change in errors. The results really were that clear-cut for one type of test, the psychomotor maze. For other tests, such as choice reaction time, both drugs affectes speed and errors, but the differences in relative effects were inb the same direction. For more details on the alcohol research, click here.

Another study (Tiplady et al., 2005) compared temazepam with the alpha-2 stimulant clonidine. There were two striking differences in the performance effects. The first was that clonidine, thoiugh clearly sedative, had little effect on memory consolidation (that is the formation of new long-term memories). Temazepam, as expected, caused substantial impairment, as does alcohol. On the other hand, clonidine had a particularly marked effect on the arrow flanker task, supporting the idea that adrenaline has a particular role to play in avoiding distraction. 

In an unpublished study, (Duarte et al. 2008) we have compared two inhaled anaesthetics, sevoflurane and nitrous oxide, with ethanol. Sevoflurance was much more sedative than nitrous oxide relative to its anaesthetic potency, but much less analgesic.

These are just a few pieces of a complex jig-saw puzzle, that will take a long while to complete!