Dopamine decreases NMDA currents in the oval bed nucleus of the stria terminalis of cocaine self-administering rats.
Dopamine (DA) and N-methyl-D-aspartate receptors (NMDARs) contribute in the neural processes underlying drug-driven behaviors. DA is a potent modulator of NMDAR, but few studies have investigated the functional interaction between DA and NMDAR in the context of substance abuse. We combined the rat model of cocaine self-administration with brain slice electrophysiology to study DA modulation of NMDA currents in the oval bed nucleus of the stria terminalis (ovBNST), a dense DA terminal field involved in maintenance of cocaine self-administration amongst other drug related behaviors. Long-Evans rats self-administered intravenous cocaine (0.75 mg/kg/injection) on a progressive ratio (PR) schedule of reinforcement for 15 days and whole-cell patch-clamp recordings were done on the 16th day. DA reduced NMDA currents in brain-slices from cocaine self-administering rats, but not in those of drug-naïve and sucrose self-administering, or when cocaine exposure was passive (yoked), revealing a mechanism unique to voluntary cocaine intake. DA reduced NMDA currents by activating G-protein-coupled D1- and D2-like receptors that converged on phospholipase C and protein phosphatases. Accordingly, our study reveals a mechanism that may contribute to dysfunctional synaptic plasticity associated with drug-driven behaviors during acute withdrawal.
Department of Biomedical and Molecular Sciences, Center for Neuroscience Studies, Queen's University, 99 University Avenue, Kingston, Ontario K7L 3N6, Canada.
Michal
M
Krawczyk
Department of Biomedical and Molecular Sciences, Center for Neuroscience Studies, Queen's University, 99 University Avenue, Kingston, Ontario K7L 3N6, Canada.
Julian
J
deBacker
Department of Biomedical and Molecular Sciences, Center for Neuroscience Studies, Queen's University, 99 University Avenue, Kingston, Ontario K7L 3N6, Canada.
Xenos
X
Mason
Department of Biomedical and Molecular Sciences, Center for Neuroscience Studies, Queen's University, 99 University Avenue, Kingston, Ontario K7L 3N6, Canada.
Andrea A
AA
Jones
Department of Biomedical and Molecular Sciences, Center for Neuroscience Studies, Queen's University, 99 University Avenue, Kingston, Ontario K7L 3N6, Canada. Electronic address: eric.dumont@queensu.ca.
Eric C
EC
Dumont
D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012646:Self Administration; D012686:Septal Nuclei / Q000187:drug effects*; D013395:Sucrose / Q000008:administration & dosage
D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D018683:Excitatory Amino Acid Agents; D016194:Receptors, N-Methyl-D-Aspartate; C034883:guanosine 5'-O-(2-thiotriphosphate); D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013395:Sucrose; D003042:Cocaine; D004298:Dopamine
Brain slice electrophysiology; Cocaine; Dopamine; NMDA; Self-administration