title: Changes in levels of D1, D2, or NMDA receptors during withdrawal from brief or extended daily access to IV cocaine.
abstract: We previously reported that brief (1 h), but not extended (6 h), daily access to cocaine results in a sensitized locomotor response to cocaine and in elevated c-Fos immunoreactivity and DAT binding in the nucleus accumbens (N.Acc) core. In order to better our understanding of the neural adaptations mediating the transition from controlled drug use to addiction, the current experiments were set to further explore the neural adaptations resulting from these two access conditions. Rats received either brief daily access to saline or cocaine, or brief daily access followed by extended daily access to cocaine. Subjects were then sacrificed either 20 min, or 14 or 60 days, after the last self-administration session. Samples of the ventral tegmental area (VTA), N.Acc core and shell, dorsal striatum, and medial prefrontal cortex (mPFC) were taken for analysis of D1 ([3H]SCH-23390), D2 ([3H]Spiperone), and NMDA ([3H]MK-801) receptor binding (using the method of receptor autoradiography). At 20 min into withdrawal, D2 receptors were elevated and NMDA receptors were reduced in the mPFC of the brief access animals while D1 receptors were elevated in the N.Acc shell of the extended access animals, compared to saline controls. D2 receptors were reduced in the N.Acc shell of the brief access animals compared to saline controls after 14 days, and compared to extended access animals after 60 days of withdrawal. In summary, extended access to cocaine resulted in only transient changes in D1 receptors binding. These results suggest that the development of compulsive drug use is largely unrelated to changes in total binding of D2 or NMDA receptors.
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychology, University of California, Santa Barbara, CA 93106-9660, USA. shahar@psych.ucsb.edu
authors.forename: Osnat
authors.initials: O
authors.lastname: Ben-Shahar
authors.forename: Patrick
authors.initials: P
authors.lastname: Keeley
authors.forename: Mariana
authors.initials: M
authors.lastname: Cook
authors.forename: Wayne
authors.initials: W
authors.lastname: Brake
authors.forename: Megan
authors.initials: M
authors.lastname: Joyce
authors.forename: Myriel
authors.initials: M
authors.lastname: Nyffeler
authors.forename: Rebecca
authors.initials: R
authors.lastname: Heston
authors.forename: Aaron
authors.initials: A
authors.lastname: Ettenberg
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D004334:Drug Administration Schedule; D018698:Glutamic Acid / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018765:Dopamine Uptake Inhibitors; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D003042:Cocaine; D004298:Dopamine