title: Baseline-dependent effects of cocaine pre-exposure on impulsivity and D2/3 receptor availability in the rat striatum: possible relevance to the attention-deficit hyperactivity syndrome.
abstract: We have previously shown that impulsivity in rats predicts the emergence of compulsive cocaine seeking and taking, and is coupled to decreased D2/3 receptor availability in the ventral striatum. As withdrawal from cocaine normalises high impulsivity in rats, we investigated, using positron emission tomography (PET), the effects of response-contingent cocaine administration on D2/3 receptor availability in the striatum. Rats were screened for impulsive behavior on the five-choice serial reaction time task. After a baseline PET scan with the D2/3 ligand [(18)F]fallypride, rats were trained to self-administer cocaine for 15 days under a long-access schedule. As a follow-up, rats were assessed for impulsivity and underwent a second [(18)F]fallypride PET scan. At baseline, we found that D2/3 receptor availability was significantly lower in the left, but not right, ventral striatum of high-impulsive rats compared with low-impulsive rats. While the number of self-administered cocaine infusions was not different between the two impulsivity groups, impulsivity selectively decreased in high-impulsive rats withdrawn from cocaine. This effect was accompanied by a significant increase in D2/3 receptor availability in the left, but not right, ventral striatum. We further report that D2/3 receptor availability was inversely related to baseline D2/3 receptor availability in the ventral striatum of high-impulsive rats, as well as to the left and right dorsal striatum of both low-impulsive and high-impulsive rats. These findings indicate that the reduction in impulsivity in high-impulsive rats by prior cocaine exposure may be mediated by a selective correction of deficient D2/3 receptor availability in the ventral striatum. A similar baseline-dependent mechanism may account for the therapeutic effects of stimulant drugs in clinical disorders such as ADHD.
authors: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors: Daniele
authors: D
authors: Caprioli
authors: Young T
authors: YT
authors: Hong
authors: Stephen J
authors: SJ
authors: Sawiak
authors: Valentina
authors: V
authors: Ferrari
authors: David J
authors: DJ
authors: Williamson
authors: Bianca
authors: B
authors: Jupp
authors: T
authors: T
authors: Adrian Carpenter
authors: Franklin I
authors: FI
authors: Aigbirhio
authors: Barry J
authors: BJ
authors: Everitt
authors: Trevor W
authors: TW
authors: Robbins
authors: Tim D
authors: TD
authors: Fryer
authors: Jeffrey W
authors: JW
authors: Dalley
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism* / Q000517:prevention & control; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage*; D007175:Impulsive Behavior / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012646:Self Administration
chemical_list: D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D003042:Cocaine
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