Reward pathways/systems

The nucleus accumbens is part of the limbic system. It receives dopaminergic input through the mesolimbic system that originates from cell bodies in the ventral segmental area (A 10 cell group). This mesolimbic dopaminergic pathway is part of the reward pathways. Drugs of abuse (cocaine, amphetamine, opiates or nicotine) have been shown to increase the level of dopamine release in these neurons. 

O Virtually all abused substances appear to activate the same brain reward pathway. Key components of the reward pathway are the dopamine (DA) mesocorticolimbic system that projects from the ventral tegmental area (VTA) and the nucleus accumbens (NA) to the prefrontal cortex, the amygdala, and the olfactory tubercle (Figs. 33-3 and 33-4).5 Animal studies... 

These dopaminergic reward pathways are critical for normal survival, since they provide the pleasure drives for eating, drinking and reproduction. However, this system produces similar sensations of pleasure with alcohol, cocaine, heroin, nicotine,... 

Cannabinoids may share at least some common neuronal mechanisms with opioid compounds. Studies of intracellular events associated with ligand binding to either cannabinoid or opiate receptors indicate that these receptors are linked via G proteins to the production of cAMP. Certain studies have also indicated that there may be some interaction between cannabinoid binding sites and opiate receptors in the reward pathway. In addition, there is increasing evidence that cannabinoids interact with opiate systems involved in the perception of pain. In fact, cannabinoids clearly produce analgesic effects in both experimental animals and humans, and of all the potential clinical uses of cannabinoids, the mediation of analgesia has received the most attention. Some evidence also indicates that the cannabinoid receptor system is an analgesic system. 

On the basis of this in vivo SPECT study, the authors speculated that marijuana may interact with dopaminergic systems in brain reward pathways. 

Both cocaine and the amphetamines act through the monoamine neurotransmitter systems, particularly by enhancing dopaminergic activity. This action in the brain s reward pathways may account for the highly addictive nature of cocaine. 

Accumulating electrophysiological and neuroanatomical analyses indicate that some of the CB, CNR receptor is targeted to the presynaptic terminals of neurons where it acts to inhibit release of classical neurotransmitters as reviewed by Elphick and Egertova, (2001). It is therefore tempting to speculate that the endocannabinoid system may be a major player in the reward pathway, particularly as it is one of the most abundant neurochemical systems in the CNS. Other studies report that THC, the major psychoactive constituent in marijuana, inhibits the synaptosomal uptake of dopamine, serotonin, norepinephrine, acetylcholine, and GABA. This, therefore, warrants pre-clinical evaluations to determine the role(s) of the endocannabinoid system in dmg and alcohol dependence and other neuropsychiatric conditions. 

The mesolimbic dopaminergic system is the principal reward pathway in the brain. Amphetamine, cocaine, and opiates cause dopamine release in the nucleus accumbens. Food seeking and sexual behavior do so as well. 

Dopamine is the neurotransmitter that is most implicated in addictive behaviors. Drug addictions occur more readily in people who have inherited an abnormal dopamine receptor, for example. It is also a major transmitter in the reward pathway of the brain. Pleasurable activities such as eating and sex, release dopamine, so in terms of evolution, behaviors that promote human survival activate our built-in reward system. 

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