Addiction is a state characterized by compulsive engagement in rewarding stimuli, despite adverse consequences.
There has been significant advancement in understanding the structural changes that occur in parts of the brain involved in the reward pathway (mesolimbic system) that underlies addiction.
[3] Most research has focused on two portions of the brain: the ventral tegmental area, (VTA) and the nucleus accumbens (NAc).
[5] Drugs of abuse increase the VTA's ability to project dopamine to the rest of the reward circuit.
GABA is an inhibitory neurotransmitter that decreases the probability that the target neuron will send a subsequent signal.
The effects of drugs of abuse on the ventral tegmental area (VTA) and the nucleus accumbens (NAc) have been studied extensively.
The effect of these structural changes on behavior is uncertain and studies have produced conflicting results.
In response to drugs of abuse, structural changes can be observed in the size of neurons[22] and the shape and number of the synapses between them.
Opiates and stimulants produce opposite effects in structural plasticity in the reward pathway.
[citation needed] Opiates decrease spine density and dendrite complexity in the nucleus accumbens (NAc).
[25] Stimulants increase spinal density and dendritic complexity in the nucleus accumbens (NAc),[21][23][26][27] ventral tegmental area (VTA),[28] and other structures in the reward circuit.
[23][26][27] There are neurons with cell bodies in the VTA that release dopamine onto specific parts of the brain, including many of the limbic regions such as the NAc, the medial prefrontal cortex (mPFC), dorsal striatum, amygdala, and the hippocampus.
Exposure to drugs of abuse elicits LTP at excitatory synapses on VTA dopamine neurons.
[6] Excitatory synapses in brain slices from the VTA taken 24 hours after a single cocaine exposure showed an increase in AMPA receptors in comparison to a saline control.
[33] This effect of inducing LTP in VTA slices 24 hours after drug exposure has been shown using morphine, nicotine, ethanol, cocaine, and amphetamines.
[42] These neurons project inhibitory connections to the VTA and receive excitatory input from various other structures in the limbic system.
Changes in the excitatory synaptic inputs into these neurons have been shown to be important in mediating addiction-related behaviors.
[44] Unlike the VTA, a single dose of cocaine induces no change in potentiation in the excitatory synapses of the NAc.
[10] This suggests that the structural changes in the NAc are associated with long-term behaviors (rather than acute responses) associated with addiction such as drug seeking.
[46] Neuroscientists studying addiction define relapse as the reinstatement of drug-seeking behavior after a period of abstinence.
Theoretically, if the structural changes in the brain associated with addiction can be blocked, then the negative behaviors associated with the disease should never develop.