Lack of effects of guanfacine on executive and memory functions in healthy male volunteers
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Guanfacine is an α2-adrenergic receptor agonist that has been shown to have beneficial effects on working memory and attentional functions in monkeys and in patients with attention deficit hyperactivity disorder.
The aim of this study was to further investigate the cognitive-enhancing properties of guanfacine using an established battery of tasks measuring executive and memory functions.
Sixty healthy male volunteers were randomised into three groups. Cognitive testing was performed from +2 to +4 h after double-blind administration of a single oral dose of 1 or 2 mg of guanfacine or placebo.
Systolic blood pressure was significantly reduced by both doses of guanfacine at the end of the testing session. There were no statistically significant effects on any of the cognitive measures. Two trend effects were observed with poorer performance on digit span backward and slower ‘Go’ reaction times after guanfacine.
This study found no improvement of prefrontal memory or executive functions after guanfacine. Negative effects on blood pressure and trend effects on digit span backward and go reaction time indicate a mild sedative effect of guanfacine at these doses, possibly via mechanisms of autoreceptor down-regulation.
KeywordsAlpha receptor Guanfacine Noradrenaline Memory Prefrontal
- Arnsten AFT, Robbins TW (2002) Neurochemical modulation of prefrontal function in humans and animals. In: Stuss DT, Knight RT (eds) Principles of frontal lobe function. Oxford University Press, New York, pp 51–84Google Scholar
- Arnsten AF, Cai JX, Goldman-Rakic PS (1988) The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes. J Neurosci 8:4287–4298Google Scholar
- Avery RA, Franowicz JS, Studholme C, van Dyck CH, Arnsten AF (2000) The alpha-2A-adrenoceptor agonist, guanfacine, increases regional cerebral blood flow in dorsolateral prefrontal cortex of monkeys performing a spatial working memory task. Neuropsychopharmacology 23:240–249CrossRefPubMedGoogle Scholar
- Bond A, Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47:211–218Google Scholar
- Chappell PB, Riddle MA, Scahill L, Lynch KA, Schultz R, Arnsten A, Leckman JF, Cohen DJ (1995) Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette's syndrome: preliminary clinical experience. J Am Acad Child Adolesc Psychiatry 34:1140–1146CrossRefPubMedGoogle Scholar
- Howell D (2001) Statistical methods for psychology. Wadsworth, BelmontGoogle Scholar
- Lezak MD, Howieson DB, Loring DW, Hannay HJ, Fischer JS (2004) Neuropsychological assessment, 4th edn. Oxford University Press, New YorkGoogle Scholar
- Logan GD, Zbrodoff NJ, Fostey AR (1983) Costs and benefits of strategy construction in a speeded discrimination task. Mem Cogn 11:485–493Google Scholar
- Overtoom CCE, Verbaten MN, Kemner C, Kenemans JL, van Engeland H, Buitelaar JK, van der Molen MW, van der Gugten J, Westenberg H, Maes RA, Koelega HS (2003) Effects of methylphenidate, desipramine and l-dopa on attention and inhibition in children with ADHD. Behav Brain Res 145:7–15CrossRefPubMedGoogle Scholar
- Robbins TW, James M, Owen AM, Sahakian BJ, Lawrence AD, McInnes L, Rabbitt PM (1998) A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: implications for theories of executive functioning and cognitive aging. J Int Neuropsychol Soc 4:474–490CrossRefPubMedGoogle Scholar
- Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, Hopwood A, Wallace C, Deakin JF, Sahakian BJ, Robbins TW (1999) Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology 146:482–491PubMedCrossRefGoogle Scholar
- Sagar HJ (1999) Clinicopathological heterogeneity and non-dopaminergic influences on behavior in Parkinson's disease. In: Stern GM (ed) Parkinson's disease [advances in neurology 80]. Lippincott Williams & Wilkins, Philadelphia, pp 409–417Google Scholar
- Scahill L, Chappell PB, Kim YS, Schultz RT, Katsovich L, Shepherd E, Arnsten AF, Cohen DJ, Leckman JF (2001) A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry 158:1067–1074PubMedCrossRefGoogle Scholar