Addiction
reward system, leaving the person feeling depressed and unable to enjoy things they previously had. 179 The drug is then required just to attain the normal levels of dopamine function; 180 this is substance dependence. Larger amounts of the drug then need to be taken to achieve the dopamine high the drug user had previously wanted. This is called tolerance. Tolerance in the short term can partly be explained by a molecule called CREB, or cAMP response element-binding protein. This is a transcription factor, which is a protein that regulates the expression of genes. When a drug is taken, cells which respond to the high levels of dopamine produce a signalling molecule called cAMP, which activates CREB. CREB then causes certain genes to be expressed, resulting in production of the proteins those genes code for. Some of these proteins dampen the effects of the reward circuitry, for example dynorphin, which inhibits some of the neurons in the VTA so that the same feelings of pleasure are not felt as much by the person. Sustained drug use therefore leads to high levels of CREB, leading to the dampening of the reward system and the manifestation of tolerance. 181 However, levels of CREB will fall after only a few days of abstinence from the drug, so this cannot be the cause of long-term addiction. Another transcription factor may be the answer, however. The levels of delta FosB have been shown to increase gradually in mice
and rats due to chronic drug use, and stay high for many months. 182 These studies suggested that the high levels of this molecule led to hypersensitivity to the drugs in the animals, so that the animals relapsed into the addiction after long periods of abstinence. One possible suggestion for the mechanism of this hypersensitivity is that the delta FosB caused the neurons in the nucleus accumbens to grow more dendritic spines, so that they could receive more information. 183 This may explain why the brain would overreact in such a way after a drug was reintroduced after a long time. However, the full biological mechanisms of addiction are still unknown, and research is still ongoing. Findings like this could provide new areas to focus on in the treatment for addiction. Current treatments are failing to completely cure most addicts, but knowing exactly how neural interactions and changes cause addiction could help us to find better, more effective treatments. Understanding that addiction is more than just a behavioural choice but an actual form of brain disease could change how society approaches the treatment and management of addicts. Ultimately, though, a greater understanding of the neural underpinnings of addiction could also help to us to understand how our behaviour is related to brain function in general, and perhaps even provide an insight into the nature of human thought, mental processes or even consciousness itself.
179 (NIDA, 2010) 180 (Ibid.) 181 (Nestler & Malenka, op. cit.)
182 ( Ibid.) 183 (Ibid.)
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