Neuroscience Online

Section I: Cellular and Molecular Neurobiology 12. Biogenic Amine Neurotransmitters Part 10 of 11 Jack C. Waymire, Ph.D.

Dopamine - Physiological and Behavioral Actions

DA appears to be involved in at least two phases of motivated behavior: an appetite phase and a consumption phase. The ventral striatum, particularly the nucleus accumbens, has been shown to be actively involved in appetitive aspects of motivation. For example, food deprived animals with lesions of the nucleus accumbens fail to show an appetitive behavior when presented with food. The consumption of the food, in contrast, is unimpaired by these lesions. On the other hand, the dorsal striatum, particularly the caudate-putamen, appears to be involved in consummatory aspects of motivated behavior. Lesions in this region disrupt motivated behavior. Animals with lesions in this region will approach food but will not consume it. These and other observations have led to the proposition that DA mediates a performance activating effect of motivated behavior, as well as conveying internal reward signals. These characteristics of DA neurotransmission make it an extremely important neurotransmitter in motivational behavior as well as in the neuropharmacology of reward. Importantly, DA neurotransmission is hypothesized to be at the heart of the mechanisms of ALL addictive-drugs and behaviors. A pertinent example of DA's role is illustrated by both cocaine and amphetamine, two abused drugs that act by increasing the concentration of DA in the synaptic space.

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Norepinephrine - Physiological and Behavioral Actions

NE neurons appear to be involved in the regulation of an organism's vigilance. The broad projection of the locus coeruleus (LC) makes it especially well suited to act as a mechanism to alert cortical and thalamic areas to incoming sensory stimuli. The LC is electrophysiologically quiet during low vigilance states such as sleep or in the lack of sensory input. When exposed to a strong stimulus, the LC markedly increases its firing rate, however. The broad influence of the activated LC is to filter weak stimuli and enhance moderate stimuli. This filtering and enhancement by NE is believed to aid in CNS processing of sensory information. In support of this conclusion, the application of NE to cortical neurons reduces responsiveness to weak stimuli, and enhances responses to strong stimuli. a₂ receptors appear to be important for these responses.

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Serotonin - Physiological and Behavioral Actions

Serotonin is important in the regulation of appetite, and appears to act in a pathway that monitors the carbohydrate intake, acting as a negative regulator of the motivation to ingest carbohydrate. This response appears to be mediated by 5-HT in the hypothalamus and has led to the use of serotonin uptake blockers, such as fenfluramine, as obesity pills (Table VII).

Many clinical observations and animal behavioral studies support the conclusion that serotonin is an important factor in aggressive behavior and the expression of dominance versus submissive behavior. For example the use of pharmacological agents to decrease levels of 5-HT at synapses in animal studies consistently demonstrates that low 5-HT is associated with both increased aggressiveness and decreased dominance. Similarly, the measurement of 5-HT metabolites in CSF and blood of patients or experimental animals shows that low 5-HIAA predicts aggressiveness as well as risk taking and a lower social rank. This correlation between decreased 5-HT activity and increased aggression was recently supported by the observation that 5-HT_1B receptor knock-out mice have a marked increase in aggressive behavior.

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