Amphetamine also possesses the ability to inhibit the enzymes monoamine oxidase A and B (MAO-A and MAO-B) in high doses. MAO-A is responsible for the break down of serotonin, dopamine, norepinephrine, and epinephrine. MAO-B is responsible for breaking down dopamine (more potently than MAO-A) and phenylethylamine (PEA), which has actions similar to amphetamine itself, and is thought to be involved in feelings of lust, confidence, obsession, and sexuality. Some of the first antidepressants successfully marketed are in fact Monoamine-Oxidase inhibitors. However, MAO inhibition seen with amphetamine is not substantial enough in duration and quantity to entail the need for a tyramine-limited diet, unlike the more potent and long lived MAO-inhibiting antidepressants.

Amphetamine's ability to cause the inhibition of MAO results in the accumulation of monoamines: amphetamine directly stimulates the release of these neurochemicals, resulting in a potent elevation in monoamine neurotransmission. In sum, the effect of amphetamines is to increase neurotransmitter availability in the synapse, by both releasing more neurotransmitters, as well as prolonging their availability in the synapse by slowing their removal.

possible mechanisms of action of adderall:
* dopamine reuptake inhibition

Dextroamphetamine induces more euphoria, whereas levoamphetamine induces more depression

dextroamphetamine = S(+) isomer

"Amphetamines are believed to exert their effects by binding to the monoamine transporters and increasing extracellular levels of the biogenic amines dopamine, norepinephrine, and serotonin."

"It is hypothesized that D-amphetamine acts primarily on the dopaminergic (DA) systems, while L-amphetamine is comparatively norepinephrinergic (NE). The primary reinforcing and behavioral-stimulant effects of amphetamine, however, are linked to enhanced dopaminergic activity, primarily in the mesolimbic dopaminergic pathway. Amphetamine binds to the dopamine transporter (DAT) and blocks the transporter's ability to clear DA from the synaptic space. In addition, amphetamine is transported into the cell, which leads to dopamine efflux (DA is transported out of the cell and into the synaptic space via reverse transport of the DAT)."


mesolimbic dopaminergic pathway
http://en.wikipedia.org/wiki/Mesolimbic_pathway

"The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex. It is known to be involved in modulating behavioral responses to stimuli that activate feelings of reward (motivation) and reinforcement through the neurotransmitter dopamine.[1]"

mesolimbic dopaminergic pathway
begins in the ventral tegmental area of the midbrain
connects to the limbic system via the nucleus accumbens, amygdala, hippocampus, medial prefrontal cortex

"Studies have shown that rats that had their ventral tegmental area and nucleus accumbens destroyed do not lose their learning capabilities, but rather lack the motivation to work for a reward." [5]

[5] # ^ a b Berridge KC. 2007. The debate over dopamine's role in reward: the case for incentive salience. Psychopharmacology 191:391-431

mesolimbic dopaminergic pathway:
    ventral tegmental area: *ventral-tegmental-area
    nucleus acumbens:
        location: ventral striatum
        characteristics:
        - medium spiny neurons
            - # ^ Zhang TA, Maldve RE, Morrisett RA. 2006. Coincident signaling in mesolimbic structures underlying alcohol reinforcement. Biochemical Pharmacology 72:919-27
            - # ^ Purves D et al. 2008. Neuroscience. Sinauer 4ed. 754-56
        shell: #limbic region
        core: #motor region
        medium spiny neurons:
            receive-input-from:
                dopaminergic neurons of the VTA
                glutamatergic neurons of the hippocampus
                glutamatergic neurons (?) of the amygdala
                glutamatergic neurons of the medial prefrontal cortex
            output-GABA-to:
                ventral pallidium: #part of the basal ganglia