Dopamine and the reward pathway
How does cocaine activate the mesolimbic pathway?
It binds to dopamine transporters in the nucleus accumbens, thus preventing dopamine reuptake. This results in increased dopamine-mediated transmission in the NAcc.
Where is the mesolimbic pathway found?
It connects the ventral tegmental area (VTA) to the nucleus accumbens (NAcc).
What are the neurochemical changes underlying the transition into addiction?
THERE IS A TRANSITION FROM POSITIVE REINFORCEMENT TO NEGATIVE REINFORCEMENT -There are two reward systems: the reward system which relays between the VTA and NAcc (DA and GABA used as neurotransmitters), and the anti-reward system which relays between the amygdala and the brainstem (noradrenaline and CRF used as neurotransmitters) -The anti-reward system play a major role in activating the adverse effects of withdrawal -As well as activating the reward system, potentially addictive drugs suppress the anti-reward system -In non-dependent individuals, drug use predominantly acts on the reward system -However, repeated use leads to downregulation of the reward system, and thus the anti-reward system becomes the predominant system -Thus drug use becomes supported by negative reinforcement - i.e. the drug is taken to suppress the anti-reward system and thus alleviate withdrawal symptoms rather than to activate the reward system and produce pleasurable effects
How do amphetamines activate the mesolimbic pathway?
They bind to dopamine transporters in the nucleus accumbens, thus preventing dopamine reuptake. In addition, they are able to enter dopaminergic nerve terminals in the NAcc and stimulate the release of additional dopamine from synaptic vesicles. Both mechanisms result in increased dopamine levels, bringing about an increase in transmission in the NAcc.
What is the role of dopamine in the reward pathway?
-A dopamine response encodes information about the value and context of a reward -In 2010, Schultz proposed that signals the difference between prediction and actual occurrence of reward - REWARD-PREDICTION ERROR -It has been shown in monkeys that an unpredicted reward leads to increased dopaminergic firing -A predicted reward leads to no change in dopaminergic firing -An unpredicted lack of reward leads to a decrease in dopaminergic firing
How do opioids activate the mesolimbic pathway?
-By binding to opioid receptors in the nucleus accumbens -This results in increased dopamine release -There are also dopamine-independent mechanisms implicated in the action of opioids on the mesolimbic pathway
How does alcohol activate the mesolimbic pathway?
-There is an increase of dopamine release in the nucleus accumbens -This is perhaps an indirect effect of alcohol's GABA-enhancing effects -There are also dopamine-independent ways in which alcohol promotes reinforcement - for example, it also causes increased release of opioid peptides (endorphins) in the ventral tegmental area, amygdala and nucleus accumbens
How do cannabinioids activate the mesolimbic pathway?
By binding to cannabinoid receptors on dopaminergic neurons of the ventral tegmental area and the nucleus accumbens. This results in depolarisation; the neurone is activated and this results in release of dopamine as a neurotransmitter.
How does nicotine activate the mesolimbic pathway?
By binding to nAChRs of dopaminergic neurons of the ventral tegmental area and the nucleus accumbens. This results in depolarisation; the neurone is activated and this results in release of dopamine as a neurotransmitter.
