Orquestic regulation of neurotransmitters on reward-seeking behavior

Abstract

The ventral tegmental area is strongly associated with the reward system. Dopamine is released in areas such as the nucleus accumbens and prefrontal cortex as a result of rewarding experiences such as food, sex, and neutral stimuli that become associated with them. Electrical stimulation of the ventral tegmental area or its output pathways can itself serve as a potent reward. Different drugs that increase dopamine levels are intrinsically rewarding. Although the dopaminergic system represent the cornerstone of the reward system, other neurotransmitters such as endogenous opioids, glutamate, γ-Aminobutyric acid, acetylcholine, serotonin, adenosine, endocannabinoids, orexins, galanin and histamine all affect this mesolimbic dopaminergic system. Consequently, genetic variations of neurotransmission are thought influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. Here, we discuss current evidence on the orquestic regulation of different neurotranmitters on reward-seeking behavior and its potential effect on drug addiction.

Keywords: Dopamine; Drug addiction; Endocannabinoids; Galanin; Histamine; Orexin; Reward-seeking behavior; Serotonin.

Figure 1

Dopaminergic system and reward processing. Dopaminergic neurons are located in the midbrain structures substantia nigra (SNc) and the ventral tegmental area (VTA). Their axons project to the striatum (caudate nucleus, putamen and ventral striatum including nucleus accumbens), the dorsal and ventral prefrontal cortex. The mesolimbic dopamine pathway mediates the psychopharmacology of reward, whether that is a natural high or a drug-induced high, and is sometimes referred to as the pleasure center of the brain, with dopamine as the pleasure neurotransmitter.

Figure 2

Neurotransmitter regulation of reward-seeking behavior. The common pathway of reward-seeking behavior in the brain is the mesolimbic dopamine pathway. This pathway is modulated by many naturally occurring substances in the brain in order to deliver normal reinforcement to adaptive behaviors (such as eating, drinking, sex) and thus to produce “natural highs,” such as feelings of joy or accomplishment. These neurotransmitter inputs to the reward system include the brain’s own morphine/heroin (i.e., endorphins such as enkephalin), the brain’s own cannabis/marijuana (i.e., anandamide), the brain’s own nicotine (i.e., acetylcholine), and the brain’s own cocaine/amphetamine (i.e., dopamine itself), among others. The numerous psychotropic drugs of abuse that occur in nature bypass the brain’s own neurotransmitters and directly stimulate the brain’s receptors in the reward system, causing dopamine release and a consequent “artificial high.” Thus alcohol, opiates, stimulants, marijuana, benzodiazepines, sedative hypnotics, hallucinogens, and nicotine all affect this mesolimbic dopaminergic system.