The Dark Side of Neuroplasticity

Although neuroplasticity may sound like a sci-fi superpower, it is one of the key mechanisms our brains use to keep us alive and functioning, despite the diverse stimuli they encounter daily. Plasticity takes the form of functional or structural reorganisation, allowing the brain to adapt to events ranging from traumatic brain injury to learning a new skill. 

Two central mechanisms which enable the brain to adapt to changes in our environment are neuronal regeneration and functional reorganisation. The former is an adaptation that occurs when a synapse changes or a new neuron forms, while the latter involves undifferentiated regions of the cerebral cortex taking over functions that were carried out by the damaged region. Within synaptic plasticity, long-term potentiation describes an increase in synaptic strength because of repeated stimulation of the neuron. While examining a rabbit hippocampus, neuroscientist Timothy Bliss and physiologist Terje Lømo (1973) found that the repetitive stimulation of presynaptic fibres (transmitting electrical impulses towards the synapse) resulted in high responses of the postsynaptic neuron (receiving the electrical impulse) — lasting longer than anticipated, therefore ‘long-term’ potentiation. When this postsynaptic neuron is stimulated, an increase in the release of neurotransmitters occurs. This triggers the postsynaptic neuron to increase the number of receptors available to receive these signals, becoming more sensitive to their presence. As a result, the threshold for the neuron to generate the electrical signal to the next neuron is lowered, making it easier for these signals (action potentials) to fire. This is one mechanism by which the brain gains said plasticity: changing the neurotransmitters and receptors — and therefore the threshold — to adapt to a stimulus.

At this point, we have learned a few of the sci-fi-like transformations that the brain can make use of in case of an environmental change. However, like any physiological mechanism, it has its downsides when exogenous (and inherently harmful) substances make their way into the inner workings. Plasticity can turn maladaptive when a dysfunctional reorganisation occurs, generating a plethora of detrimental symptoms. Repeated exposure to addictive substances (including cocaine, alcohol, and opioids) results in compulsive engagement — dictated by a memory trace that is exhibited by the activation of brain circuits as a type of reflex action. The mesolimbic dopamine pathway is activated when an individual engages in a rewarding activity, causing a release of dopamine that leads to pleasure, reinforces the behaviour, and promotes its repetition. However, the problem arises when substances hijack the system, causing unnaturally high rushes of dopamine, generating a system of desensitisation. Tolerance is built up as an adaptation to such high levels of dopamine, reducing receptor sensitivity to this neurotransmitter, so increasing reliance on these artificial methods to feel a crumb of satisfaction.

Dr Yavin Shaham studied relapse mechanisms through drug-taking in rats that were trained to self-administer cocaine (as unethical as this sounds), providing evidence for the plastic nature of the brain. A retractable lever could be pressed to deliver the substance (via injection).  After a ten-day training session, the rats were withdrawn from cocaine for differing lengths of time. Once this withdrawal period ended, the lever was present, but no drug injection occurred. Interestingly, researchers noticed that rats that had been deprived of the drug for 60 days pressed the lever around 200 times in a six-hour time frame compared to the 50 times for a one-day withdrawal period. The relapse effect appears stronger, as the rats are more eager to acquire the substance, suggesting that neural circuits supporting cue-drug association are not only still present after 60 days, but are strengthened over time — directly pointing to neuroplasticity. These results were consistent with human observations, suggesting that a delayed-onset craving syndrome develops in the first two months of abstinence, making individuals most vulnerable to relapse at times beyond the acute phase of withdrawal.

Addiction is, on a fundamental level, a maladaptive neural mechanism driven by the dopamine reward system and the brain’s plasticity to substances. The evidence provided here reminds us that, as for most baseless stigmas, the “lack of willpower” ascribed to individuals suffering from substance addiction is a false and unfounded label.

Image from Wikimedia Commons