title: Psychostimulants affect dopamine transmission through both dopamine transporter-dependent and independent mechanisms.
abstract: The precise mechanisms by which cocaine and amphetamine-like psychostimulants exert their reinforcing effects are not yet fully defined. It is widely believed, however, that these drugs produce their effects by enhancing dopamine neurotransmission in the brain, especially in limbic areas such as the nucleus accumbens, by inducing dopamine transporter-mediated reverse transport and/or blocking dopamine reuptake though the dopamine transporter. Here, we present the evidence that aside from dopamine transporter, non-dopamine transporter-mediated mechanisms also participate in psychostimulant-induced dopamine release and contribute to the behavioral effects of these drugs, such as locomotor activation and reward. Accordingly, psychostimulants could increase norepinephrine release in the prefrontal cortex, the latter then alters the firing pattern of dopamine neurons resulting in changes in action potential-dependent dopamine release. These alterations would further affect the temporal pattern of dopamine release in the nucleus accumbens, thereby modifying information processing in that area. Hence, a synaptic input to a nucleus accumbens neuron may be enhanced or inhibited by dopamine depending on its temporal relationship to dopamine release. Specific temporal patterns of dopamine release may also be required for certain forms of synaptic plasticity in the nucleus accumbens. Together, these effects induced by psychostimulants, mediated through a non-dopamine transporter-mediated mechanism involving norepinephrine and the prefrontal cortex, may also contribute importantly to the reinforcing properties of these drugs.
authors.affiliation: Departments of Pharmaceutical and Administrative Sciences, Loma Linda University Schools of Pharmacy and Medicine, Loma Linda, CA 92350, USA. Electronic address: idelapena@llu.edu.
authors.forename: Ike
authors.initials: I
authors.lastname: Dela Peña
authors.affiliation: Departments of Pharmaceutical and Administrative Sciences, Loma Linda University Schools of Pharmacy and Medicine, Loma Linda, CA 92350, USA.
authors.forename: Ruzanna
authors.initials: R
authors.lastname: Gevorkiana
authors.affiliation: Departments of Pharmaceutical and Administrative Sciences, Loma Linda University Schools of Pharmacy and Medicine, Loma Linda, CA 92350, USA; Basic Sciences, Loma Linda University Schools of Pharmacy and Medicine, Loma Linda, CA 92350, USA. Electronic address: wshi@llu.edu.
authors.forename: Wei-Xing
authors.initials: WX
authors.lastname: Shi
mesh_terms: D000200:Action Potentials; D059331:Adrenergic Neurons / Q000187:drug effects / Q000378:metabolism; D000661:Amphetamine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000378:metabolism / Q000494:pharmacology*; D003042:Cocaine / Q000378:metabolism / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009473:Neuronal Plasticity; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine
keywords: Dopamine neuron; Dopamine transporter; Firing pattern; Oscillations; Prefrontal cortex; Psychostimulants