Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin
Top Cited Papers
- 2 November 2000
- Vol. 39 (1) , 32-41
- https://doi.org/10.1002/1098-2396(20010101)39:1<32::aid-syn5>3.0.co;2-3
Abstract
A large body of evidence supports the hypothesis that mesolimbic dopamine (DA) mediates, in animal models, the reinforcing effects of central nervous system stimulants such as cocaine and amphetamine. The role DA plays in mediating amphetamine-type subjective effects of stimulants in humans remains to be established. Both amphetamine and cocaine increase norepinephrine (NE) via stimulation of release and inhibition of reuptake, respectively. If increases in NE mediate amphetamine-type subjective effects of stimulants in humans, then one would predict that stimulant medications that produce amphetamine-type subjective effects in humans should share the ability to increase NE. To test this hypothesis, we determined, using in vitro methods, the neurochemical mechanism of action of amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), (+)-methamphetamine, ephedrine, phentermine, and aminorex. As expected, their rank order of potency for DA release was similar to their rank order of potency in published self-administration studies. Interestingly, the results demonstrated that the most potent effect of these stimulants is to release NE. Importantly, the oral dose of these stimulants, which produce amphetamine-type subjective effects in humans, correlated with the their potency in releasing NE, not DA, and did not decrease plasma prolactin, an effect mediated by DA release. These results suggest that NE may contribute to the amphetamine-type subjective effects of stimulants in humans. Synapse 39:32–41, 2001. Published 2001 Wiley-Liss, Inc.Keywords
This publication has 45 references indexed in Scilit:
- Psychological and Cardiovascular Effects and Short-Term Sequelae of MDMA (“Ecstasy”) in MDMA-Naïve Healthy VolunteersNeuropsychopharmacology, 1998
- Hormonal Responses to d- and d,l-Fenfluramine in Healthy Human SubjectsNeuropsychopharmacology, 1996
- Evaluation of Phentermine and Fenfluramine, Alone and in Combination, in Normal, Healthy VolunteersNeuropsychopharmacology, 1996
- Evaluation of the abuse liability of aminorexDrug and Alcohol Dependence, 1994
- Differential effects of the enantiomers R(−) and S(+) oxaprotiline on major endogenous depression, the sleep EEG and neuroendocrine secretion: Studies on depressed patients and normal controlsEuropean Neuropsychopharmacology, 1993
- Identification of a GBR12935 homolog, LR1111, which is over 4,000‐fold selective for the dopamine transporter, relative to serotonin and norepinephrine transportersSynapse, 1993
- Flunarizine attenuates cocaine-induced inhibition of A9 dopaminergic neuronsPharmacological Research, 1991
- The dopamine hypothesis of the reinforcing properties of cocaineTrends in Neurosciences, 1991
- Blockade of the Noradrenaline Carrier Increases Extracellular Dopamine Concentrations in the Prefrontal Cortex: Evidence that Dopamine Is Taken up In Vivo by Noradrenergic TerminalsJournal of Neurochemistry, 1990
- Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reactionBiochemical Pharmacology, 1973