Systemic administration of a dopamine, but not a serotonin or norepinephrine, transporter inhibitor reinstates cocaine seeking in the rat.
Reinstatement of cocaine-seeking behavior can be elicited by a systemic priming injection of cocaine or a non-selective biogenic amine transporter inhibitor. In order to determine which biogenic amine is responsible for this effect, selective dopamine (GBR 12909), serotonin (fluoxetine) or norepinephrine (nisoxetine) transporter inhibitors were systemically administered in order to assess their ability to induce cocaine seeking in rats. Administration of GBR 12909, but not nisoxetine or fluoxetine, dose-dependently reinstated cocaine seeking in rats. Furthermore, administration of the non-selective dopamine receptor antagonist flupenthixol into the nucleus accumbens shell attenuated GBR 12909-induced reinstatement of cocaine seeking. These results suggest that increases in extracellular concentrations of dopamine, specifically in the nucleus accumbens shell, are primarily responsible for promoting cocaine priming-induced reinstatement of drug seeking in rats.
Schmidt
Heath D
HD
Laboratory of Neuropsychopharmacology, Department of Pharmacology, L-603, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA. donmar@bu.edu
Pierce
R Christopher
RC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D004298:Dopamine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D012701:Serotonin / Q000008:administration & dosage*
D004791:Enzyme Inhibitors; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine