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 |
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| Authors: | 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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| Affiliation: | 1.Behavioural and Clinical Neuroscience Institute, University of Cambridge,, Cambridge, UK;2.Department of Psychology, University of Cambridge, Cambridge, UK;3.Department of Clinical Neurosciences, University of Cambridge, Wolfson Brain Imaging Centre, Cambridge Biomedical Campus, Cambridge, UK;4.Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK |
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| 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 [18F]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 [18F]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was not different between the two impulsivity groups, impulsivity selectively decreased in high-impulsive rats withdrawn from cocaine.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. |
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| Keywords: | nucleus accumbens dopamine psychostimulants positron emission tomography addiction attention-deficit hyperactivity disorder |
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