Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of rat.
Evidence recently provided has suggested a specific involvement of the GABAergic system in modulating positive reinforcing properties of several drugs of abuse through an action on mesolimbic dopaminergic neurons. The GABA(B) receptor agonist baclofen has been proposed as a potential therapeutic agent for the clinical treatment of several forms of drug addiction. In the present study, using the in vivo microdialysis technique, we investigated the effect of baclofen on nicotine, cocaine, and morphine-induced increase in extracellular dopamine (DA) levels in the shell of the nucleus accumbens, a brain area supposedly involved in the modulation of the central effects of several drugs of abuse, of freely moving rats. As expected, nicotine (0.6 mg/kg s.c.), morphine (5 mg/kg s.c.), and cocaine (7.5 mg/kg i.p.) administration in rats induced a marked increase in extracellular DA concentrations in the nucleus accumbens, reaching a maximum value of +205 +/- 8.4%, +300 +/- 22.2%, and +370 +/- 30.7%, respectively. Pretreatment with baclofen (1.25 and 2.5 mg/kg i.p.) dose-dependently reduced the nicotine-, morphine-, and cocaine-evoked DA release in the shell of the nucleus accumbens. Furthermore, baclofen alone did not elicit changes in basal DA extracellular levels up to 180 min. Taken together, our data are in line with previous reports demonstrating the ability of baclofen to modulate the mesolimbic DAergic transmission and indicate baclofen as a putative candidate in the pharmacotherapy of polydrug abuse.
Fadda
Paola
P
B.B.Brodie Department of Neuroscience, University of Cagliari, 09042 Monserrato, Cagliari, Italy. pfadda@unica.it
Scherma
Maria
M
Fresu
Alessandra
A
Collu
Maria
M
Fratta
Walter
W
D000818:Animals; D001418:Baclofen / Q000494:pharmacology* / Q000627:therapeutic use; D003042:Cocaine / Q000037:antagonists & inhibitors; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D058786:GABA-B Receptor Agonists; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000037:antagonists & inhibitors; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000037:antagonists & inhibitors; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism; D012201:Reward; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D009538:Nicotine; D009020:Morphine; D001418:Baclofen; D003042:Cocaine; D004298:Dopamine