SONGWRITERS frequently compare love and addiction. Addicts compare wanting drugs to wanting sex. And scientists who study addiction are now beginning to agree with both.
Stimulants like cocaine act on the brain’s dopamine system, and so mimic the thrill of desire and anticipation. Depressant drugs like heroin, on the other hand, produce the opposite kind of pleasure – a dreamy satiation and freedom from pain, caused by their action on the brain’s opioid system.
A speedball, a cocktail of cocaine and heroin, can be likened to a rapid, hyped-up sex simulation, moving rapidly from desire to climax. Because of this powerful ability to simulate the most intense thrills, it is often said that drugs can hijack the brain’s pleasure, reward and motivation systems, leaving addicts overwhelmed by craving for the drug, and willing to do anything for their next fix.
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It’s racy parallels like these that have led a few intrepid souls to stake their reputations on the idea that we could perhaps learn more about addiction by studying sex and love than the drugs themselves. If we want to know how drugs derail our pleasure and reward systems, we first need to know what those systems are, and how they behave. According to neuroscientist Annarose Childress, what those systems usually do is control our sexual behaviour.
Childress, of the University of Pennsylvania, is one of a group of researchers who believe the reward system must have evolved to get animals interested in sex. “This circuitry has been well preserved throughout evolution to enable animals to eat and reproduce,” she says. “Those functions have been around long before cocaine and opiates.” To understand addiction, we need to find a way to study these parts of the brain as they do what comes naturally.
Not surprisingly, it’s been quite tricky persuading funding bodies and universities of the potential benefits of showing pornography to brain-scan volunteers, allowing people to misbehave inside a scanner, or measuring sex hormone levels during drug taking. But a few researchers have done it. They argue that if we know the anatomy and chemistry of normal sexuality, perhaps we could find how addiction starts to drive behaviour and how desire turns into cravings that addicts simply can’t ignore. Perhaps understanding our sex drive will one day provide the key to treating addiction.
Studies of animals have given researchers good reason to suspect that there is a link. One recent study on rodents, for example, likens the bond between mates to an addiction.
Larry Young, a behavioural neuroscientist at the Yerkes National Primate Center in Atlanta, says that high levels of a receptor called V1aR in a brain region called the ventral pallidum are associated with monogamous behaviour in one type of vole; other voles with fewer of these receptors seek multiple partners. It seems as though the monogamous voles get more pleasure from their partners, while the promiscuous voles get more joy from novelty. The ventral pallidum also plays a part in reward and addiction. The region is active when rodents learn to give themselves shots of drugs and when they are in places they associate with getting their fix.
Monogamous male voles seem to become addicted to a particular female, says Young, perhaps associating her with some sort of rewarding feelings in the same way that animals may come to associate a place with the rewarding sensation of drugs.
“The neural circuits underlying addiction did not evolve to respond to drugs,” he says. “Drugs simply modulate the natural reward circuits that have evolved to ensure that animals do all the things that they should do, such as eating, sex and forming social attachments.”
When you have such compelling animal models, and sex and drugs are so frequently mentioned in the same breath, it’s surprising that it has taken so long to make similar comparisons in the human brain. Yet just this month two different groups of researchers told the annual meeting of the Society for Neuroscience in Orlando that brain regions implicated in addiction are also active during arousal, orgasm and ejaculation.
The delay has not just been because of the technical difficulties of doing experiments. It took Mario Beauregard from the Neurological Institute of the University of Montreal three years to get some of the first studies that imaged sexual arousal in the brain published. More than one highbrow journal told him the findings were “not of general interest”. His latest study, which appeared this year in Human Brain Mapping (vol 16, p 1) uses functional magnetic resonance imaging (fMRI) to explore which brain areas become activated when men and women view erotic films.
Not surprisingly, the visual areas are busy, but so too are many evolutionarily ancient circuits associated with emotion – the limbic system, anterior temporal pole and amygdala, and a region of the orbitofrontal cortex (OFC). Previous research found that these areas are important in prioritising, decision making and giving emotional colour to an experience, and may subconsciously trigger physiological responses and desire.
Just last year, Childress revealed that these same circuits were also critical in cocaine addiction. Just as with sexual desire, strong feelings can be triggered by what people see – needles or crack pipes can induce strong craving, even in addicts who’ve been clean for years. But addicts find it much harder to control their desires than most jilted lovers confronted with a picture of their ex. So while Beauregard has been trying to understand how these circuits regulate our emotions, Childress has been trying to see how they work in addicts’ brains.
Beauregard’s group used fMRI to image men’s brains. In one experiment the men were shown porn films, and sometimes asked to try to inhibit their arousal; at other times they were encouraged to enjoy it. In another study the men were asked either to control or wallow in feelings of sadness. When they inhibited their emotions, the limbic activity disappeared totally, while higher brain areas such as the cortex – especially in the frontal lobes – remained active.
Childress suggests that the same might be true for controlling a desire for drugs. She finds that when addicts learn to fight their cravings by considering the damage drugs could do, activity in the OFC goes up, but declines in the amygdala. “The OFC is important for putting on the brakes, looking at consequences,” she says. She has already found that cocaine addicts have less grey matter in their OFC than non-addicts – but whether the missing matter makes people vulnerable to addiction or is caused by drugs is unclear. The next step is to compare people who can control their sexual behaviour or drug use with those who cannot, in the hope of rooting out the essence of compulsive behaviour and self-control – and how it can be influenced by drugs.
And it’s not just looking at the way the brain is wired for sex and love that’s giving addiction researchers a few leads. The complex mix of neurochemicals and hormones involved might give some useful information about how addicts could be helped to control their desires too. One important chemical is dopamine. The common pathway affected by drugs of abuse is the dopamine system linked to a brain region called the nucleus accumbens. Whether it’s nicotine, cocaine, heroin or alcohol, the more directly or profoundly a drug affects the dopamine system, the more craving and pleasure it produces.
Addicts appear to have some differences in their dopamine systems. For example, recent studies by Nora Volkow and her team at the Brookhaven National Laboratory in New York found that many addicts seem to have fewer dopamine receptors than non-addicts. There is also some suggestion that certain gene variations may make neural signalling via dopamine less effective in addicts. Both problems might predispose people to seek ways of boosting an underactive pleasure system, making drugs especially attractive.
But while addiction researchers have pitched dopamine as the brain’s best dope and key to all joy, it might not be that simple. Dopamine’s main brain function, in fact, seems to be controlling movement rather than mood – which is why the progressive loss of dopamine neurons in people with Parkinson’s disease primarily causes movement disorders, not an inability to feel pleasure. But the two aren’t entirely separate. Wanting to feel good cannot be disentangled from the motivation to create that feeling. “When you think about it, it makes sense that when you are attracted to things, your natural instinct is to move towards them,” says Jim Pfaus, a psychologist who studies dopamine and sexual behaviour at Concordia University in Canada.
Dopamine is also released in anticipation of a reward – it rises when addicts see cocaine, when people see tempting food and during sexual desire, so it may be more linked to believing reward is close than to signalling satisfaction. Or it may correspond to different aspects of pleasure when expressed in different parts of the brain. Pfaus is now studying the chemical sequence that plays out as an animal moves from desire to satiation during mating, in an attempt to fully understand this relationship.
One surprise has been that dopamine responses seem to vary between males and females, at least in rats. Could there be differences in the way men and women become addicted too? It’s a consideration addiction research has neglected for too long, thinks Jill Becker, a psychologist at the University of Michigan.
In male rats, she says, dopamine levels go up when they smell a female, see her or have sex. “Anything to do with being introduced to a female, dopamine goes up,” she says. But female rats only get a “hit” of dopamine when they can control sex. That scenario doesn’t usually happen with caged animals, but in the wild, females normally allow the male near, then flee, returning a few times, before they will eventually accept his advances.
This “pacing” ensures the rat is optimally primed for pregnancy. A release of oestrogen sensitises the dopamine system, so it will give her a “kick”, and simultaneously maximises the odds of successful conception.
“In terms of drug addiction,” says Becker, “most work has been done in males.” It’s not hard to argue that in men drugs may simply take over the reward system and replace the drive for sex with a drive for drugs, she says.
Male addicts may pursue drugs with the single-mindedness with which other men pursue sex; getting high gives them the sense that they are on track to getting satisfaction, so they do it again. Repeating this sequence may make it harder and harder to stop. “But,” says Becker, “the female is more interesting. During sex, dopamine doesn’t always go up. It requires the social and physical context to be right.” This could mean that cravings in women could vary with their hormones and that different addiction treatments may be needed for them.
Exploring the links between sexuality and addiction has also thrown up another hormone that might be critical in the reward system. Oxytocin is important in forming bonds between mates and between parents and their offspring. The hormone’s levels also spike during orgasm – and all are highly rewarding activities. Oxytocin researcher C. Sue Carter of the University of Maryland and her team found that in monogamous voles where the males help with childrearing, “good dads” have more oxytocin than promiscuous ones who love ’em and leave ’em. And low levels of oxytocin may be partly to blame when cocaine-addicted rats – and perhaps even humans – neglect their offspring.
Even more intriguing, oxytocin seems to both prevent rodents becoming tolerant to heroin and reduce the overactivity usually induced by cocaine. It even cuts heroin-withdrawal symptoms, according to Gabor Kovács and colleagues from the Markusovszky Teaching Hospital in Hungary. The oxytocin connection could explain why falling in love – which might mean raised levels of the hormone – has helped many an addict quit their habit.
So maybe love will provide a happy ending. Or perhaps it will take sex too – or at least an understanding of its chemistry and effect on the brain – to inspire new ways of treating addiction. Addiction researchers can’t afford to be prudish if they really want to understand how our brains work.
