Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration

Author: Solanto, M.V.

Description: The psychostimulants, D-amphetamine (D-AMP) and methylphenidate (MPH), are widely used to treat attention-deficit hyperactivity disorder (ADHD) in both children and adults. The purpose of this paper is to integrate results of basic and clinical research with stimulants in order to enhance understanding of the neuropharmacological mechanisms of therapeutic action of these drugs. Neurochemical, neurophysiological and neuroimaging studies in animals reveal that the facilitative effects of stimulants on locomotor activity, reinforcement processes, and rate-dependency are mediated by dopaminergic effects at the nucleus accumbens, whereas effects on delayed responding and working memory are mediated by noradrenergic afferents from the locus coeruleus (LC) to prefrontal cortex (PFC). Enhancing effects of the stimulants on attention and stimulus control of behavior are mediated by both dopaminergic and noradrenergic systems. In humans, stimulants appear to exert rate-dependent effects on activity levels, and primarily enhance the motor output, rather than stimulus evaluation stages of information-processing. Similarity of response of individuals with and without ADHD suggests that the stimulants do not target a specific neurobiological deficit in ADHD, but rather exert compensatory effects. Integration of evidence from pre-clinical and clinical research suggests that these effects may involve stimulation of pre-synaptic inhibitory autoreceptors, resulting in reduced activity in dopaminergic and noradrenergic pathways. The implications of these and other hypotheses for further pre-clinical and clinical research are discussed.

Subject headings: Adult; Animals; Attention Deficit Disorder with Hyperactivity/diagnosis/drug therapy/physiopathology; Brain/drug effects/physiopathology; Central Nervous System Stimulants/adverse effects/therapeutic use; Child; Dextroamphetamine/adverse effects/therapeutic use; Humans; Methylphenidate/therapeutic use

Publication year: 1998

Journal or book title: Behavioural Brain Research

Volume: 94

Issue: 1

Pages: 127-152

Find the full text : https://www.sciencedirect.com/science/article/pii/S0166432897001757

Find more like this one (cited by): https://scholar.google.com/scholar?cites=9076490471410983550&as_sdt=1000005&sciodt=0,16&hl=en

Type: Journal Article

Serial number: 1349