Physical dependence type 2

In 1954, Olds and Milner discovered that there appeared to be pleasure spots in the brain. ⁸ Implanting electrodes in certain areas of the brain, and enabling a rat to stimulate that area by pressing on a lever that activated an electric current, produced in most brain areas nothing of note. In some brain areas, however, the rats seemed keen on the effects of self-stimulation; in some cases, if left to their own devices, they would self-stimulate to the exclusion of all else – this was most likely to happen in a degraded environment devoid of stimulation.

As mentioned, noradrenaline (norepinephrine) was discovered in the brain in 1954. In 1959, a second catecholamine, dopamine, was identified. This was shown to be deficient in patients with Parkinson’s disease. Replacement therapy, using the dopamine precursor l-dopa, brings about substantial benefits to sufferers of this disease.

The later mapping of dopamine-containing neurones showed that they originated in a discrete area – the ventral tegmentum. Some of these neurones run to strictly motor areas of the brain and constitute the nigrostriatal system. It is the loss of nerve cells in this pathway that leads to Parkinson’s disease.

Other dopamine-containing neurones run to higher areas of the midbrain and to cortical areas. It appears that these are centrally involved in what is termed incentive learning – the kind of learning that occurs when an animal encounters a biologically important stimulus such as food or a potential sexual partner.

The ventral tegmental system seems to be closely associated with the pleasure systems discovered by Olds and Milner. However, the picture has become far more complicated. It now seems that, far from there being pleasure hot spots in the brain, there are areas of the brain that respond to familiar signals pleasurably and unfamiliar signals with displeasure. Pleasure seems to be at least in part a function of the familiarity of the message being relayed through the system.

CRAVING

Why do so many alcohol or opiate users return to their addiction after detoxification? If the terror of withdrawal were such a significant factor in producing chronic abuse, it might be expected that anyone with the least bit of wit would keep well clear of further involvement. What perversity or self-destructive impulse is it that leads to further abuse?

The traditional response to this problem was to distinguish between physical dependence and psychological dependence. It is usually argued that the latter is a state of mind, one that may stem from deep-seated psychological difficulties. It is this state of mind that some people see as the real problem with the addictions. While it is relatively easy with modern technologies to take in drug addicts and ‘dry them out’, it is a much more difficult problem to ensure that they remain drug-free.

When asked why they return to their habits, the usual response from sufferers is in terms of cravings. The notion of cravings seems to suggest a depravity or perversity in keeping with the social opprobrium accorded to addicts. It suggests some weakness on their part that fits in with the idea they have psychological difficulties. Current research suggests that this picture is quite wrong. ⁹

It seems, increasingly, that cravings are a very tangible physical reality and that the form of dependence that is characterised by cravings is in fact a physical dependence of another sort. In favour of this argument is the fact that not all drugs of abuse cause cravings. Cocaine, the amphetamines, nicotine, alcohol and the opiates notably do but LSD, phencyclidine, the psychedelic drugs generally and the benzodiazepines, antidepressants and antipsychotics do not.

BEHAVIOURAL SENSITISATION

Experimental work on drug effects on the brain has revealed that continued administration of certain drugs, far from leading to tolerance, appears to produce just the opposite effect, even when the environment is held constant. Indeed, in a mirror image of the production of tolerance, the holding of the environment constant, in these experiments, appears to facilitate the production of increasingly enhanced effects in response to certain drugs.

This phenomenon is called behavioural sensitisation. 3 and 10 Certain drugs induce it, others do not. Morphine is capable of inducing both sensitisation and tolerance within the one animal: the animal develops tolerance to some of the effects of morphine, such as analgesia, and sensitisation to others – one of which is the fact that continued intake becomes increasingly pleasurable.

Initial experiments suggested that morphine produced behavioural inactivity and was somewhat unpleasant. Animals who were linked to electrodes connected to the so-called pleasure spots in the brain were less likely to self-stimulate themselves when given morphine. This ran contrary to the popular belief that opiates are pleasurable, and in fact it can be noted that the experience of many people trying opiates for the first time is that they are not very pleasant.

Subsequent experiments demonstrated that morphine becomes increasingly pleasant to take. Chronic exposure to morphine in experimental animals gradually brings about increases in activity and self-stimulation. There is an odd aspect to this, which is that such increases are at their height some 3hours after morphine administration, in contrast to analgesia, which is at a maximum 1hour after administration. Maximal brain levels of the drug also occur 1hour, and not 3hours, after administration. Furthermore, analgesia and the respiratory depression brought about by morphine can be antagonised by morphine antagonists, such as naloxone, but the pleasurable effects of the drug are not antagonised by these agents.

APPETITES

What is happening? It appears that morphine, alcohol, cocaine and the amphetamines feed into the brain systems responsible for the generation of and satisfaction of appetites, of which the ventral tegmental system outlined above is a component part. A moment’s reflection should indicate that the last thing an appetitive system could do with is tolerance to the sight of food, drink or sex, for example – rather, just the opposite. In contrast to the effect of environmental cues in helping to bring about tolerance because they signal the non-threatening, or insignificant, nature of what is happening, environmental cues might be expected to lead to increased effects where appetites are concerned. That is, we will become increasingly sensitive to aspects of an environment that indicate the possibility of food or sex or drink. Such cues should lead to increased rather than decreased interest. Typically, however, we do not notice the accumulation of environmental prompts pushing us toward the consummation of an appetite unless we have been removed from the environment artificially for a while. Try dieting, seriously, and you will become aware of all the prompts to eat in the environment – advertisements in magazines, smells of food, cooking, etc.

The effect of public houses and the cultures surrounding both drink and drugs provide a host of small prompts, each of which prime an appetite that has already been created. This can even extend to having one’s appetite aroused by the sight of needles.