why the risk of relapse persists for years, sometimes for a lifetime. At this point you will not be surprised to learn that dopamine has been shown to play a role in long-term memory formation...
Molecular mechanisms After describing the process in general, let’ s see what happens at a molecular level( Figure 2). All the addictive drugs, with few exceptions, stimulate the release of dopamine at different levels. Some of them, like opioids, appear to have an additional reward system.
Cannabinoids increase the efflux of dopamine by their actions on CB1 receptors in GABA-ergic neurons.
Cocaine and amphetamines act on the presynaptic terminals of dopaminergic neurons. Cocaine blocks the dopamine transporter on the membrane of presynaptic terminals, causing the accumulation of extracellular dopamine. Amphetamines enter the presynaptic terminals of dopaminergic neurons through the dopamine transporter. Once in the cytoplasm they reverse the transport of dopamine out of vesicles and out of the membrane.
The effect of opioids is more complex because they can use both dopamine-dependent and dopamine-independent signals. By binding to µ receptors as to inhibit GABA-ergic interneurons, they can lift their inhibitory effect on dopaminergic neurons, favoring thus a dopamine release. Additionally, these µ receptors are found in the nucleus accumbens, thus opioids can stimulate reward circuit directly. It is interesting to mention that µ receptors are also found in the brain stem and spinal cord, where they play a critical role in modulating pain and controlling respiration, explaining therefore the analgesic effect of opiates and their susceptibility to cause respiratory arrest in case of an overdose.
Figure 2- Molecular effects of drugs
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