The specific behavioral effects of amphetamine and related compounds depend to a great extent on the task requirements, the normal frequency of the behavior, the dose, and individual characteristics. The primary reward properties of these drugs are due to their ability to enhance dopaminergic activity in a part of the limbic system called the nucleus accumbens. Amphetamine also has a mild, temporary, inhibitory action on the enzyme MAO and redistributes monoamines from the synaptic vesicles to the cytoplasm, so there are more monoamines to be released. Methamphetamines are roughly equipotent in promoting release and inhibiting reuptake and are more potent in affecting the dopamine and norepinephrine transporters than the serotonin transporter. The first mechanism binds to these transporters and inhibit monoamine reuptake into neurons and secondly, they promote reverse transport of the monoamines. Both of the mechanisms that increase the extracellular concentrations of the monoamines involve the protein transporters that normally terminate the action of monoamines via reuptake. Amphetamines and related drugs increase extracellular concentrations of the monoamines through two primary mechanisms. Cause more of the neurotransmitters to be released.Īmphetamines also increase extracellular levels of serotonin, but this action appears to play minimal role in most of its behavioral effects. Instead of amphetamines being an agonist, amphetamines have properties that enhance the level of epinephrine, norepinephrine, and dopamine in the synaptic cleft, which then increases catecholamine receptor activation with the cleft. Agonist effect occurs when a substance mimics the action of a neurotransmitter thus directly activating the receptor. Little activity appears to be due to a direct agonist action at these receptor sites.
Increase extracellular concentrations of the monoaminesĮnhance dopaminergic activity in a part of the limbic system called the nucleus accumbens Enhance levels of catacholamines in synaptic cleft