The human reward system is made up of neural structures responsible for incentive
salience (desire), associative learning (primarily positive reinforcement and classical
conditioning), and positive/pleasure emotions (e.g. euphoria).
Dopamine is the primary neurotransmitter of
the brain’s reward mechanisms
Most important reward pathway is the
mesolimbic dopamine pathway.
This connects the ventral tegmental area (VTA) of the midbrain, to the nucleus
accumbens (NAc) and olfactory tubercle, which are located in the ventral
striatum
The projections from
the VTA are a network of dopaminergic neurons with co-localized postsynaptic
glutamate receptors.
The NA itself consists mainly of GABAergic medium spiny
neurons.
When a rewarding stimulus, such as eating food, or direct stimulation
by a drug occurs, dopaminergic neurons in the VTA are activated. These neurons
project to the NAc, and their activation causes dopamine levels in the NAc to
rise, activating dopamine receptors and generating a reward response, thus
encouraging repetition and learning. –> any activity that resulted in a reward from your brain will therefore be one you want to repeat. This is essentially how your brain keeps you alive and reproducing.
Another major dopamine pathway, the
mesocortical pathway, also originates in the VTA but travels to the prefrontal
cortex, and is thought to integrate information which determines whether a
behavior will be elicited. The basolateral amygdala projects into the NAc and
is thought to also be important for motivation, while the hippocampus plays a role
in learning and memory.
Even though increased dopamine in the brain
reward system is generally thought to be the final common pathway for the
reinforcing properties of drugs, other neurotransmitters such as serotonin are
involved in the modulation of both drug self-administration and dopamine
levels. Serotonin may be important in
modulating motivational factors, or the amount of work and individual is
willing to perform to obtain a drug. Serotonergic neurons project both to the
NA and VTA and appear to regulate dopamine release at the NA.
Excessive intake of addictive drugs –> repeated release of high amounts of dopamine –>increased dopamine
receptor activation.
The intrinsic purpose of an endogenous reward center is to
reinforce behaviors that promote survival, so when a drug
stimulates this center, drug-seeking behavior is also promoted - induced by
glutamatergic projections from the prefrontal cortex to the nucleus accumbens
Prolonged and abnormally high levels of dopamine in
the synaptic cleft can induce receptor downregulation, resulting in a decrease
in the sensitivity to natural stimuli.
Alongside the positive reinforcement,
these withdrawal symptoms can be considered negative reinforcing factors.
Discontinued drug use will often induce various negative responses such as
chronic irritability, physical pain, emotional pain, malaise, dysphoria,
alexithymia, and loss of motivation for natural rewards.
Chronic addictive
drug use causes alterations in gene expression in
the mesocorticolimbic projection, which arise through transcriptional and epigenetic mechanisms. The most important transcription factors that
produce these alterations are ΔFosB, cyclic adenosine monophosphate (cAMP),
(CREB), (NF-κB). Overexpression of ΔFosB in
the D1-type medium spiny neurons in the nucleus
accumbens is necessary and sufficient for many of the neural
adaptations and behavioral effects (e.g., expression-dependent increases in
drug self-administration and reward sensitization) seen in drug
addiction. This means an individuals actual genes are changed by chronic drug use to make them even more addicted - not just a case of being able to stop when they chose.
Nobody knows the war that takes place in my mind as i walk down the street. I’ll smile back at you while thinking of suicide. I’ll carry on with life as if it weren’t full of pain. I don’t know why i am like this… Why is my mind filled with despondency?
i had a therapist once who said that these states will wax and wane. which gave my mother relief, because it meant that in the bad times, there would be good times— but it also gave her anxiety because it meant that in the good times, there would be bad times.
An x-ray showing needles that had broken off in the neck of a heroin addict. After the veins in the patient’s arms, legs, chest, abdomen and forehead had all collapsed, he began to inject himself subcutaneously. He then began to inject himself into the neck and would use the same needles until they broke off inside the skin. Broken needles inside the skin of drug users are not uncommon. One study indicated that at least 20% of drug users have experienced a needle breaking off inside the skin.
