carnitine transporter. Amphetamine is known to strongly induce cocaine- and amphetamine-regulated transcript (CART) gene expression, a neuropeptide involved in feeding behavior, stress, and reward, which induces observable increases in neuronal development and survival in vitro. The CART receptor has yet to be identified, but there is significant evidence that CART binds to a unique . Amphetamine also inhibits monoamine oxidases at very high doses, resulting in less monoamine and trace amine metabolism and consequently higher concentrations of synaptic monoamines. In humans, the only post-synaptic receptor at which amphetamine is known to bind is the receptor, where it acts as an agonist with low micromolar affinity. The full profile of amphetamine's short-term drug effects in humans is mostly derived through increased cellular communication or neurotransmission of dopamine, serotonin, norepinephrine, epinephrine, histamine, CART peptides, endogenous opioids, adrenocorticotropic hormone, corticosteroids, and glutamate, which it affects through interactions with , , , , , , and possibly other biological targets. Amphetamine also activates seven human carbonic anhydrase enzymes, several of which are expressed in the human brain. Dextroamphetamine is a more potent agonist of than levoamphetamine. Consequently, dextroamphetamine produces greater stimulation than levoamphetamine, roughly three to four times more, but levoamphetamine has slightly stronger cardiovascular and peripheral effects. Dopamine In certain brain regions, amphetamine increases the concentration of dopamine in the synaptic cleft. Amphetamine can enter the presynaptic neuron either through or by diffusing across the neuronal membrane directly. As a consequence of DAT uptake, amphetamine produces competitive reuptake inhibition at the transporter. Upon entering the presynaptic neuron, amphetamine activates which, through protein kinase A (PKA) and protein kinase C (PKC) signaling, causes DAT phosphorylation. Phosphorylation by either protein kinase can result in DAT internalization ( reuptake inhibition), but phosphorylation alone induces the reversal of dopamine transport through DAT (i.e., dopamine efflux). Amphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through an unidentified Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent pathway, in turn producing dopamine efflux. Through direct activation of G protein-coupled inwardly-rectifying potassium channels, reduces the firing rate of dopamine neurons, preventing a hyper-dopaminergic state. Amphetamine is also a substrate for the presynaptic vesicular monoamine transporter, . Following amphetamine uptake at VMAT2, amphetamine induces the collapse of the vesicular pH gradient, which results in the release of dopamine molecules from synaptic vesicles into the cytosol via dopamine efflux through VMAT2. Subsequently, the cytosolic dopamine molecules are released from