HappyMutations:

The Reward Pathway (aka Reward System, Reward Center) A circuit in the brain (or a network of neurons) that seems to be the physical counterpart of our feelings of pleasure/euphoria/hedonism. It becomes stimulated in response to actions such as:

• Drinking water
• Eating food
• Having sex
• Social interaction (inc. anticipation of positive social feedback, social status/reputation, or simply having conversations)
• Maternal love
• Romantic love (also simply seeing beautiful faces can be a trigger)
• Money (and the anticipation of)

It’s easy to imagine why animals could have evolved such a trait. However, it seems like this trait, which seems essential for our survival, can sometimes promote harm instead. We are talking here about human’s ability to “hack” this system for hir own hedonic satisfaction. Thus, you see humans overeating, getting engaged in immoral acts of sex, gambling (playing with the anticipation of money is a trigger), etc. Other, perhaps even more direct stimulants of the RP that humans have discovered, are a continuously growing list of psychoactive substances that includes:

• Nicotine (the most addictive drug in the world according to some pharmacologists)
• Cocaine
• Opiates
• Amphetamine
• Alcohol
• etc

To get an idea of how powerfully addictive these drugs can be, experiments on rodents and primates who had been taught to press a lever which results in an intravenous dose of any of the aforementioned drugs. The animals are then observed while they self-administer the drug obsessively up to the point of ignoring food and sleep, sometimes even to the point of death. Even though all addictive drugs have markedly different mechanisms of action (i.e. the mechanisms by which they induce their common psychoactive effects), scientists insist that they all ultimately produce pleasure (and can therefore lead to addiction) because they all ultimately bring a common effect: the stimulation of the RP, mediated mainly by dopamine transmission. Let’s look at the RP a bit more technically: The pathway consists of dopaminergic neurons (i.e. the neurons involved with the neurotransmitter dopamine) extending from the ventral tegmental area (VTA; this region is where dopamine is synthesised) to the nucleus accumbens (nAc), the amygdala, the hippocampus and the prefrontal cortex. We’ll mention the general functions of these brain areas in a bit. For now, take a look at the below figure and imagine the red lines to represent the extension of the dopaminergic neurons from the VTA to the other regions. Let’s now take a look at the functions of the aforementioned brain regions. amygdala: emotions NAc: motor functions prefrontal cortex: attention hippocampus: memory formation One can see how these regions can add up synergistically to create events of pleasure seeking behaviour: You somehow induce the RP. Your amygdala makes you feel euphoric emotions. Your hippocampus jumps in to take notice of cues and memorise them so that the act can be repeated. Your NAc puts forth the motor functions required to repeat the act. All these require the help of the prefrontal cortex which lets you focus on the object of pleasure and how to get more of it (by the way, by now you might be thinking that the whole RP explanation is too simple to be real – and you’re probably right, but it’s the best of what western science currently has to offer). Let’s take a look at how some addictive drugs act on this pathway: Cocaine, once described by William S. Burroughs as the most exhilarating drug in the world, is also one of those with the most direct amplification of the dopamine signal in the brain. In order to understand its mechanism of action, let’s have a very brief description of the dopamine neurotransmission (for a more descriptive explanation click here). A neural network conists of various neuronal cells connected to one another in order to be able to send signals throughout the body or parts of it. Each neuron connects to the next one via an area called the synaptic cleft. In this area between the two neurons the neurotransmitters are released by one (the “presynaptic” neuron) and picked up by the next (the “postsynaptic” neuron). In the case of dopaminergic neurons (there are also other types of neurons involved with other types of neurotransmitters) we have a neuron releasing its dopamine in the synaptic cleft, where it attaches to dopaminergic receptors on the postsynaptic neuron and so on, and one of the ultimate results of this signal is euphoria. But as dopamine is left to hang about in the synaptic cleft, attaching on receptors on the postsynaptic neuron, it is eventually picked up by proteins called dopamine transporters which reside on the presynaptic neuron in order to recycle it and have it available for further signals; a system of conservation. Well cocaine block these transporters and so dopamine can be left for longer in the synaptic cleft, signalling for longer its effects. Amphetamine, or speed, another highly addictive drug, exerts its effects by causing presynaptic neurons to fire off more dopamine in the synaptic cleft - > increased signal. Many mechanisms in our brain exist together with a negative feedback system. In the case of dopaminergic neurons, they are inhibited by another type of neurons called GABAergic neurons. GABAergic neurons are the major inhibitory neurons in the CNS, i.e. they inhibit other neurons from firing up. That’s why GABA system- affecting drugs like alcohol, barbiturates and benzodiazepines have the common sedative effect. Opioids inhibit the dopaminergic neuron-inhibiting GABAergic neurons which gives an end result of dopamine stimulation. The effects of opioids of course are also due to their acting on opioid and other types of receptors.