Baseline-dependent effects of cocaine pre-exposure on impulsivity and D 2/3 receptor availability in the rat striatum: Possible relevance to the attention-deficit hyperactivity syndrome

Daniele Caprioli, Young T. Hong, Stephen J. Sawiak, Valentina Ferrari, David J. Williamson, Bianca Jupp, T. Adrian Carpenter, Franklin I. Aigbirhio, Barry J. Everitt, Trevor W. Robbins, Tim D. Fryer, Jeffrey W. Dalley

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37 Citations (Scopus)

Abstract

We have previously shown that impulsivity in rats predicts the emergence of compulsive cocaine seeking and taking, and is coupled to decreased D 2/3 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 D 2/3 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 D 2/3 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 D 2/3 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was not different between the two impulsivity groups, impulsivity selectively decreased in high-impulsive rats withdrawn from cocaine.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 D 2/3 receptor availability in the left, but not right, ventral striatum. We further report that D 2/3 receptor availability was inversely related to baseline D 2/3 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 D 2/3 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.

Original languageEnglish
Pages (from-to)1460-1471
Number of pages12
JournalNeuropsychopharmacology
Volume38
Issue number8
DOIs
Publication statusPublished - 1 Jul 2013
Externally publishedYes

Keywords

  • addiction
  • attention-deficit hyperactivity disorder
  • dopamine
  • nucleus accumbens
  • positron emission tomography
  • psychostimulants

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