Role of monoamine pathways in attention and effort: Effects of clonidine and methylphenidate in normal adult humans

Abstract

Methylphenidate (0.65 mg/kg), clonidine (200 gg) or placebo were administered to normal adult males undertaking a dichotic monitoring task in which they were required to detect nominated target words and discriminate them from phonemic distractors. Following placebo, performance was better when attention was focused than when divided. Following clonidine, subjects were poorer and slower at discriminating targets during both divided and focused attention and subjectively were withdrawn and reported difficulties with concentration. Methylphenidate had no effect on target discrimination or response time but raised the rate of response and had marked effects on spontaneous behaviour in which an increased attention capacity was generally reported. The effects on attention of the pharmacological agents employed in this study are attributed to their effects on central monoamines. The disparity noted between objective and subjective assessments of attention is discussed in terms of the voluntary allocation of effort.The projection of the monoamine cell bodies located in the reticular formation of the brainstem (Ramon- Molinar and Nauta 1966;Nauta et al. 1969) to the cerebral cortex has been shown to have regional variations in density and in laminar distribution that are particularly prominent in primates (Morrison etal. 1982a, b; Levitt etal. 1984). Whereas the thalamic afferents to cortex are mainly localised to particular cytoarchitectonic and functional regions, the terminal fields of the monoamine afferents are distributed across both regional and functional boundaries, each monoamine having its own characteristic pattern of innervation (Morrison et al. 1978(Morrison et al. , 1981. These characteristics suggest that monoamines may have more precise roles in the regulation of cortical activity in primates than had hither to been inferred from earlier reports of a sparse and diffuse cortical innervation in the rat.Animal and clinical studies indicate that one important role of the monoamine innervation of cerebral cortex may be the control of attention (see Clark et al. 1984). We have been investigating this role in normal humans and have Offprint requests to : C.R. Clark recently reported the effect on behavioural measures of attention of the dopamine antagonist drug droperidol, and the catecholamine agonist, methylphenidate (Clark et al. 1986). In the present study, we examine the effect on auditory selective attention of methylphenidate and clonidine administered intravenously to normal volunteers. It has been shown in animals that lesion of the noradrenergic coeruleocortical pathway impairs acquisition (Robbins et al. 1982) and performance (Carli et al. 1983;Everitt et al. 1983) of discrimination behaviour. Since clonidine dampens coeruleo-cortical activity in animals (Svensson et al. 1975;Aghajanian 1982) we predicted that administration of clonidine in normal adult humans would impair discriminative capacity in a dichotic auditory attention task. The effect of methylphenidate on discriminative ability in this...

Pharmacological manipulations of arousal and memory for emotional material: effects of a single dose of methylphenidate or lorazepam

“…Naylor et al, 1985;Klorman et al, 1984;Koelega, 1993;Camp-Bruno and Herting, 1994;Oken et al, 1995;Elliott et al, 1997;Mehta et al, 2000). However, there are also reports of healthy volunteers whose performance is impaired by methylphenidate (Wetzel et al, 1981;Clark et al, 1986;Rogers et al, 1999).…”

Non-pharmacological cognitive enhancement

“…nausea, abdominal pain, dry mouth), increased diuresis, palpitations, nervousness, restlessness, and sleep disturbances and especially in studies with non-sleep deprived individuals, insomnia (Baranski and Pigeau, 1997;Caldwell et al, 1999Caldwell et al, , 2000Caldwell et al, , 2004Dinges et al, 2006;Eddy et al, 2005;Gill et al, 2006;Hart et al, 2006;Lagarde et al, 1995;Pigeau et al, 1995;Wesensten et al, 2002;Whitmore et al, 2006). For methylphenidate a frequently reported side effect (reported in 13 out of 14 trials reporting side effects) was increased heart rate, while increase in blood pressure was not consistently found (Bray et al, 2004;Brumaghim and Klorman, 1998;Clark et al, 1986;Fitzpatrick et al, 1988;Hink et al, 1978;Mehta et al, 2000;Peloquin and Klorman, 1986;Rogers et al, 1999;Strauss et al, 1984;Volkow et al, 1999aVolkow et al, , 1999bWetzel et al, 1981). Besides these, typical complaints were headache, anxiety, nervousness, dizziness, drowsiness and insomnia.…”

Methylphenidate: a review of its neuropharmacological, neuropsychological and adverse clinical effects

“…The drug generally increases activity, arousal, and talkativeness and improves mood, memory and planning (Elliott et al, 1997;Mehta et al, 2000a,b). However, there is also evidence that methylphenidate disrupts attention in healthy people (Rogers et al, 1999) and some reports of the negative subjective experiences of anxiety, dysphoria and tiredness (Clark et al, 1986;Joyce et al, 1986).…”