New perspectives from microdialysis studies in freely-moving, spontaneously hypertensive rats on the pharmacology of drugs for the treatment of ADHD.

Full Abstract

Attention deficit hyperactivity disorder (ADHD) is a common childhood psychiatric condition that is effectively treated by catecholaminergic drugs with a variety of different mechanisms and the SH rat is frequently used as a model of this disorder. In vivo microdialysis in freely-moving rats has been employed extensively to provide a better understanding of the pharmacodynamics of drugs at their sites of action. In this review, these three topics are brought together to explore the contribution of in vivo microdialysis studies in spontaneously hypertensive (SH) rats to our understanding of the neurochemical deficits in this rat strain and the actions of ADHD drugs on catecholaminergic function in the prefrontocortex (PFC), striatum and nucleus accumbens. What is revealed is that basal efflux of norepinephrine in the PFC is attenuated, whilst striatal and mesolimbic dopaminergic neurotransmission is hyperfunctional; the latter observation fits closely with the hyperactive phenotype of the SH rat. Furthermore, experiments performed with the enantiomers of amphetamine and threo-methylphenidate demonstrate that pharmacodynamic effects of drugs reported from experiments in outbred rat strains, e.g. Sprague-Dawleys, do not necessarily translate to the SH rat. When the findings are compared with the clinical efficacy of drugs used in treating ADHD, they indicate that the most efficacious drugs powerfully increase both norepinephrinergic and dopaminergic neurotransmission.

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Author information

Author/s: Heal, D J (DJ); Smith, S L (SL); Kulkarni, R S (RS); Rowley, H L (HL);

Affiliation: RenaSci Consultancy Limited, BioCity, Nottingham NG1 1GF, UK. david.heal@renasci.co.uk

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Review

Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav), published in United States. (Language: eng)

Reference: 2008-Aug; vol 90 (issue 2) : pp 184-97

Dates: Created 2008/06/09; Completed 2008/08/12;

PMID: 18456311, status: MEDLINE (last retrieval date: 11/6/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amphetamine - pharmacology
Animals
Attention Deficit Disorder with Hyperactivity - drug therapy
Disease Models, Animal
Dopamine - secretion
Humans
Methylphenidate - pharmacology

Methylphenidate - pharmacology
Microdialysis - methods
Norepinephrine - secretion
Propylamines - pharmacology
Rats
Rats, Inbred SHR
Rats, Inbred WKY

Associated Chemicals: Propylamines (0) ; Methylphenidate (113-45-1) ; Amphetamine (300-62-9) ; Norepinephrine (51-41-2) ; Dopamine (51-61-6) ; atomoxetine (83015-26-3)

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