title: Cocaine-conditioned odor cues without chronic exposure: Implications for the development of addiction vulnerability.
abstract: Adolescents are highly vulnerable to addiction and are four times more likely to become addicted at first exposure than at any other age. The dopamine D1 receptor, which is typically overexpressed in the normal adolescent prefrontal cortex, is involved in drug cue responses and is associated with relapse in animal models. In human drug addicts, imaging methods have detected increased activation in response to drug cues in reward- and habit-associated brain regions. These same methods can be applied more quantitatively to rodent models. Here, changes in neuronal activation in response to cocaine-conditioned cues were observed using functional magnetic resonance imaging in juvenile rats that were made to over-express either D1 receptors or green fluorescent protein by viral-mediated transduction. Reduced activation was observed in the amygdala and dopamine cell body regions in the low cue-preferring/control juvenile rats in response to cocaine cues. In contrast, increased activation was observed in the dorsal striatum, nucleus accumbens, prefrontal cortex, and dopamine cell bodies in high cue-preferring/D1 juveniles. The increase in cue salience that is mediated by increased D1 receptor density, rather than excessive cocaine experience, appears to underlie the transition from aversion to reward in cue-induced neural response and may form the basis for habit-forming vulnerability.
authors.affiliation: Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Lowen
authors.affiliation: Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Rohan
authors.affiliation: Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Gillis
authors.affiliation: Laboratory for Developmental Neuropharmacology, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Britta S
authors.initials: BS
authors.lastname: Thompson
authors.affiliation: Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Clara B W
authors.initials: CB
authors.lastname: Wellons
authors.affiliation: Laboratory for Developmental Neuropharmacology, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Andersen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D003216:Conditioning, Operant; D003463:Cues; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
chemical_list: D017447:Receptors, Dopamine D1
keywords: BLA, basolateral amygdala; BOLD, blood oxygenation level determination; Cocaine; Cue; D1; DSTR, dorsal striatum; Development; NAc, nucleus accumbens; Odor; PFC, prefrontal cortex; ROI, region of interest; SNc/r, substantia nigra pars compacta/reticulata; Striatum; VTA, ventral tegmental area; fMRI, functional magnetic resonance imaging; pharmacoMRI, pharmacological magnetic resonance imaging