Use of Nicotinic Receptor Agonists in Treatment of ADHD
August 25, 2015 at 10:27 PM | categories: genetics
Contents
1 Tobacco Use in ADHD subjects
There is emerging evidence that cholinergic dysregulation (in particular, of nicotinic cholinergic systems) may play a role in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) [9]. Both clinical and epidemiological experiments indicate that ADHD is associated with an increased risk and earlier age of cigarette smoking [2, 7, 8]. A higher risk of smoking correlates directly with more ADHD symptoms [2]. Furthermore, maternal smoking during pregnancy increases the risk for ADHD in the offspring (independent of ADHD in mother) [6].
2 Use of Nicotinic Receptor Agonists in Treatment of ADHD
Activating the cholinergic system can improve a host of cognitive processes (reviewed by Levin et al. [4]) including learning, spatial and working memory, processing speed and ability, inhibition, selective accuracy, detection, and overall attention. In general, using the preclinical paradigms, the effects of nicotine appear to persist with chronic administration [4]. Cholinergic pathways originating in the basal forebrain project diffusely to the cerebral cortex [1]. acetylcholine (ACh) is particularly important for normal cognitive function, including processes mediated by the prefrontal cortex that are affected in ADHD, such as attention, working memory, and executive function. Additionally, nicotinic acetylcholine receptor (nAChR) stimulation can modulate dopaminergic neurotransmision [5, 10]. In animal experiments, nicotine produces a concentration dependent release of dopamine (DA) from slices of rat striatum [10], and nicotine has been shown to have effects on striatal presynaptic dopamine transporters (DATs) in adults with ADHD [3]. However, not all neuronal nAChR agonists reproduce the effects of nicotine on dopamine release.
Longitudinal data continue to highlight the chronicity and clinical and public health importance of ADHD and its treatment throughout the lifespan [11]. Unfortunately, many of the treatments for ADHD result in residual cognitive symptoms. Hence, treatment strategies that include adequate treatment of the general ADHD triad, and more specifically the attentional-based and executive function symptoms of ADHD are needed [11]. Nicotinic cholinergic neurotransmission plays an important role in attention and exectuve function processes, and nicotine has demontrated procognitive effects in a number of animal studies, and pilot data indicates some degree of efficacy in small proof-of-concept adult ADHD trails [11]. Although adverse effects associated with nicotine preclude its development as a therapeutic, a number of novel α4β2 nAChR agonists with improved safety/tolerability profiles have been discovered [11].
Acronyms
- ACh
- acetylcholine
- ADHD
- attention-deficit/hyperactivity disorder
- DAT
- dopamine transporter
- DA
- dopamine
- nAChR
- nicotinic acetylcholine receptor
References
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