Using one or more examples, explain effects of neurotransmission on human behaviour (for example, the effect of noradrenaline on depression).

Biochemistry - Dopamine and Addiction:

Summary:
The neurotransmitter explanation for addiction suggests that the cause of addiction is linked to dopamine functioning. Put simply, people use drugs to increase dopamine. The reward centre of the brain (mesolimbic pathway) contains lots of dopamine receptors. Rewarding experiences e.g. drug taking; stimulate the mesolimbic pathway releasing dopamine telling the brain that it is good J Repeated dopamine eventually causes down-regulation and leads to unpleasant withdrawal symptoms. The person continues to smoke/gamble to get rid of withdrawal symptoms. The frontal cortex is now less effective at making decisions and judging the consequences of actions - so they cannot make decisions as well and may relapse. Addicts have now learned to expect rewarding experiences from the drug. Other stimuli, e.g. cues such as the room the addict use to take the drug act as secondary reinforces for the drug. When the addict experiences them some dopamine is released and they expect a reward, even if they know it is not coming.

Initiation:
In the centre of the brain sits the reward pathway, which is responsible for driving our feelings of motivation, reward and behaviour. Your memory tells you that a particular behaviour will make you feel good; the brain tells the body to initiate the behaviour. Special neurons in the reward pathway release the chemical dopamine (VTA), which gives you a sense of pleasure. In addition, the reward pathway is responsible for making sure you repeat the behaviour. It does this by connecting to regions of the brain that control memory and behaviour. This increases the likelihood that you will repeat the behaviour. When the reward pathway signals the brains motor centre, it strengthens the wiring for behaviours that help you achieve your reward. The Reward Pathway and associated areas of the Brain: Prefrontal Cortex (PFC); Ventral Tegmental Area; Nucleus Accumbens; Amygdala

Maintenance:
Addictive behaviours and addictive substances can induce change in the structure and function of the reward systems neurons that can be shown, using PET scans to last for weeks and months. These changes contribute to tolerance, dependence and craving. The VTA sends neuron projections into the medial forebrain connecting to the amygdala and PFC. Stimulation of these areas collectively, produces pleasure and reinforcement of that behaviour. Most drugs (such as nicotine which is a psychoactive drug) and activities such as gambling release dopamine into the NA area, prompting incentive to continue and increase the behaviour. The PFC function, which normally controls decision-making and inhibits risky behaviours, is impaired in addicts, allowing them to choose immediate rewards even in the face of long-term negative consequences. Continued over-production of dopamine leads to desensitisation in receptors to compensate. This leads to increased desire to engage in the addictive behaviour to return to the same level of dopamine high i.e. the individual is becoming tolerant.

Relapse:
The VTA NA pathways also link to other areas of the brain including the memory areas and help make addicts highly sensitive to reminders of past highs, vulnerable to relapse when stressed and unable to control the urge to repeat the addictive behaviour.

Video Links:

Dopamines role in reward: http://www.youtube.com/watch?v=Ql_wAovRKO8 Dopamine & Glutamate in addiction: http://www.youtube.com/watch?v=op0XqgWQn7E&feature=related Nicotine addiction: http://www.youtube.com/watch?v=yd46Hs7pTow Nicotine withdrawal: http://www.youtube.com/watch?v=HlcIKekEldg&feature=related

Tutorial/Activities: Dopamine & Addiction: New Science of Addiction section: http://learn.genetics.utah.edu/content/addiction/ Drugs that alter the brains reward pathways: http://learn.genetics.utah.edu/content/addiction/drugs/mouse.html Genetics & the Brain: http://learn.genetics.utah.edu/content/addiction/

Some Research Studies:

J Volkow et al (2001) gave Ritalin, which gently lifts dopamine levels, to a group of

adult volunteers. Some of them loved the feeling of the drug, but others hated the way it made them feel. They then produced scans of their brains and found that those who liked the rush from the drug had fewer dopamine D2 receptors than those who hated it. Volkow et al concluded that some people are particularly vulnerable to the added rush given by dopamine-enhancing drugs, but others have a dopamine circuitry that cannot take additional stimulation. This would explain why some people after experimenting with drugs, might go on to develop an addiction while others, and given the same initial experience would not.

J Caine et al. (2007) found that mice engineered to lack a particular brain receptor for

dopamine do not develop a taste for the drug cocaine, which both humans and mice generally find highly addictive. Mouse brain cells usually carry five dopamine receptors, but mice modified to lack the one known as D1 do not self-administer, cocaine when given the chance to do so. Normal mice, by contrast will keep returning for more. The researchers admit that the implications of this study for an understanding of addiction in humans are as yet unclear, however, it does reinforce the claim that dopamine plays a key role in addiction.

J Sex Addiction and Dopamine:

Botwick and Bucci (2008) describe the treatment of a young adult male patient who was addicted to sex. He had a strong appetite for pornography in his late teens he engages in phone sex via credit cards, and in his twenties would spent up to eight hours a day online, search for sexually gratifying activity. After presenting to a psychiatrist at age 24, he was treated with nalextrone, which effectively blocked the release of dopamine associated with his online sexual activities. Blocking the reward extinguished the addictive power of that behaviour. As a result, his compulsion plummeted and his psychosexual functioning dramatically improved.

Evaluation Points:
General evaluation points for the dopamine explanation for addiction A problem for the neurochemical explanations of addiction is that they neglect other possible determining factors including the social context of alcohol or drug-taking behaviours (are reductionist). However, regarding drug addiction as a disease of the brain creates the possibility that it may be treated by various pharmacological methods. Such an approach is certainly more progressive than those that treat drug addicts as delinquents who must be punished. Is dopamine sensitivity and addiction inevitably linked? Grant et al (1998) conducted an experiment with monkeys. They showed that dopamine system could be influenced by social interactions. Animals that lost social status also lost D2 receptors. This has implications for human beings as well, particularly those whose lives are characterised by poverty and stress. Volkow (2003) suggests that those people who grow up in stimulating, engaging surroundings are protected against addiction. She argues that even if people do not have a naturally responsive dopamine system, if they have more chances to get excited about natural stimuli, they are less likely to need an artificial boost from alcohol or drugs.

Biochemistry Drugs and Dopamine:

L-Dopa was a breakthrough in treatment for Parkinsons disease, a degenerative condition that usually involves a resting tremor, a difficulty initiating movement, and difficulty in controlling directed movement such as picking up a spoon or a cup. The drug designed to relieve these symptoms because it was believed that increasing the amount of dopamine available would have a positive effect. It was initially very effective, but the effects do not usually last as the brain adapts to the presence of the drug (as addiction maintenance section above). Other treatments have been developed more recently such as the implantation into the brain of a device that can stimulate the release of dopamine in relevant areas, according to a patients individual needs. This results in fewer side effects. Some evidence for the dopamine theory of schizophrenia comes from the discovery that patients who were overmedicated for Parkinsons disease started to develop some of the positive (additional) symptoms of schizophrenia, such as hallucinations and delusions. It has also been noted that patients who were being medicated with tranquilisers that reduced the amount of dopamine available were less likely to experience these symptoms. In turn over-medication with anti-psychotic drugs was often found to lead to a condition known as tardive dyskinesia, which describes the same kind of movement problems found in Parkinsons disease. Thus it appears that there is a balance of dopamine required in individuals, and on one hand, too much dopamine can lead to symptoms of schizophrenia which on the other hand, too little can lead to difficulties with movement. Links: Video of Surgery to help hand tremor: http://news.bbc.co.uk/1/hi/7665747.stm New York Times: Health Article on L-Dopa: http://health.nytimes.com/health/guides/disease/parkinsons-disease/levadopa-(ldopa).html Parkinsons Disease: Good video talking about all aspects: http://www.uctv.tv/shows/Parkinsons-Disease-A-Dose-of-Hope-18008 Science Daily article on Dopamine Hypothesis explanation for Schizophrenia: http://www.sciencedaily.com/articles/d/dopamine_hypothesis_of_schizophrenia.htm Article on Parkinsons and Schizophrenia: http://www.uncrediblehallq.net/2008/06/29/parkinsons-and-schizophrenia/