Document Detail


Electrophysiological evidence for a reciprocal interaction between amphetamine and cocaine-related drugs on rat midbrain dopaminergic neurons.
MedLine Citation:
PMID:  10051759     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To determine the functional interactions occurring between amphetamine and cocaine-like drugs on a single neuron, we used intracellular single-electrode voltage-clamp recordings from dopaminergic cells of the rat midbrain maintained in vitro. In the presence of cocaine (3-30 microM), the outward current caused by amphetamine (100 microM) on cells held at about -60 mV was attenuated. The degree of attenuation of the amphetamine-induced response was almost the same for 3 and 30 microM cocaine (44 and 51% of control, respectively). This effect of cocaine was reversible. We also tested other DA-uptake inhibitors (nomifensine and 4-phenyltetrahydroisoquinoline) against the amphetamine-induced outward current. Both drugs enhanced the effects of dopamine (DA) while reducing the outward response caused by amphetamine. Pretreatment of the animals with reserpine (12 mg/kg/i.p.), which irreversibly depletes the vesicular DA stores, neither affected the amplitude of the current caused by amphetamine nor changed the cocaine-induced attenuation of the membrane responses to amphetamine. Interestingly, when amphetamine (3 microM) was superfused on the dopaminergic neurons prior and during the application of cocaine, the DA-uptake blocker was no longer able to potentiate the outward response caused by the superfusion of DA. Taken together, these data suggest that: (i) amphetamine and cocaine interact with the DA transporter to produce distinct actions which under certain circumstances can compete with each other; (ii) the amphetamine-induced release of DA from the somata and dendrites of the dopaminergic cells is, at least in part, related to the reverse operation of the DA transporter and is not dependent on the integrity of the vesicular content of the catecholamine.
Authors:
M Scarponi; G Bernardi; N B Mercuri
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The European journal of neuroscience     Volume:  11     ISSN:  0953-816X     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-04-21     Completed Date:  1999-04-21     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  FRANCE    
Other Details:
Languages:  eng     Pagination:  593-8     Citation Subset:  IM    
Affiliation:
IRCCS S. Lucia, Rome, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic Uptake Inhibitors / pharmacology
Amphetamine / pharmacology*
Animals
Carrier Proteins / physiology
Cocaine / pharmacology*
Dopamine / physiology
Dopamine Plasma Membrane Transport Proteins
Dopamine Uptake Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Drug Interactions
Electrophysiology
Female
Male
Membrane Glycoproteins*
Membrane Potentials / drug effects
Membrane Transport Proteins*
Mesencephalon / cytology*
Nerve Tissue Proteins*
Neurons / chemistry,  drug effects*,  physiology
Nomifensine / pharmacology
Patch-Clamp Techniques
Rats
Rats, Wistar
Reserpine / pharmacology
Chemical
Reg. No./Substance:
0/Adrenergic Uptake Inhibitors; 0/Carrier Proteins; 0/Dopamine Plasma Membrane Transport Proteins; 0/Dopamine Uptake Inhibitors; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Nerve Tissue Proteins; 24526-64-5/Nomifensine; 300-62-9/Amphetamine; 50-36-2/Cocaine; 50-55-5/Reserpine

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