Locomotor sensitization and decrease in [3H]mazindol binding to the dopamine transporter in the nucleus accumbens are delayed after chronic treatments by GBR12783 or cocaine.
Rats were treated once daily for 15 consecutive days with either cocaine or the specific dopamine uptake inhibitor 1-[2- (diphenylmethoxy)ethyl]-4-(3-phenyl-2-(propenyl)-piperazine (GBR12783) at a dose (10 mg/kg) that given acutely increases locomotor activity. Two or 14 days after the last administration, the motor stimulant responses of rats to a challenge dose (5 mg/kg) of the drug administered previously were compared with the motor stimulant responses of rats daily injected with solvent. A sensitization to the acute stimulant locomotor effect of these drugs was only observed 14 days after cessation of chronic treatments. After this withdrawal period, autoradiographic analysis revealed a significant decrease in the desipramine-insensitive [3H]mazindol binding to the dopamine transporter in the shell of the nucleus accumbens. No change was noticed in other regions with high dopamine content: core of nucleus accumbens, striatum, olfactory tubercle, substantia nigra and ventral tegmental area. Absence of concomitant decrease in [3H]dihydrotetrabenazine labeling, which indicates lack of effect on vesicular monoamine transporters, suggests that the decrease in accumbal [3H]mazindol binding did not result from a cytotoxic effect on corresponding dopamine neurons. In addition, 14 days after the last administration of GBR12783, the levels of dopamine and metabolites (dihydroxy-phenylacetic acid, homovanillic acid) and the ability of acute GBR12783 to synergize with haloperidol-induced increase in these metabolites were not modified either in the whole nucleus accumbens or in the striatum.
Boulay
D
D
Unité de Neuropsychopharmacologie Expérimentale, URA 1969 du Centre National de la Recherche Scientifique, Institut Fédératif de Recherche Multidisciplinaire sur les Peptides, Faculté de Médecine et de Pharmacie de Rouen, Saint Etienne du Rouvray, F
Duterte-Boucher
D
D
Leroux-Nicollet
I
I
Naudon
L
L
Costentin
J
J
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008454:Mazindol / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; C039737:1-(2-(diphenylmethoxy)ethyl)-4-(3-phenyl-2-propenyl)piperazine; D008454:Mazindol; D003042:Cocaine