Methylphenidate-induced impulsivity: pharmacological antagonism by β-adrenoreceptor blockade

Abstract

Noradrenaline—dopamine interactions mediate increases in locomotor activity, development of sensitisation and subjective effects of psychostimulant drugs. However, the modulatory effects of noradrenaline on psychostimulant-induced impulsivity are less clear. This article examined the relative roles of noradrenaline and dopamine in the modulation of methylphenidate-induced impulsive responding in rats performing the 5-choice serial reaction time task. Experiment 1 examined the systemic antagonism of methylphenidate-induced impulsivity with either propranolol, a β-adrenoreceptor blocker, or prazosin, an α1-adrenoreceptor antagonist, which antagonises the locomotor activating effects of amphetamine. Propranolol completely abolished methylphenidate-induced impulsivity. This effect was centrally rather than peripherally mediated, as nadolol, a peripheral β-blocker failed to affect methylphenidate-induced premature responding. Prazosin partially attenuated the methylphenidate-mediated increase in premature responding. A second experiment examined the effects of selective anti-DβH saporin-induced cortical noradrenaline depletion on methylphenidate-induced impulsivity. Contrary to the effects of β-adrenoreceptor blockade, cortical noradrenergic depletion did not alter methylphenidate-induced impulsivity. Other experiments examined the comparative effects of selective dopamine and serotonin receptor blockade. D4 dopamine receptor blockade with systemically administered L-745,870 also attenuated methylphenidate-induced impulsivity. The other antagonists had no effect on methylphenidate-induced impulsivity. Taken together, these studies provide evidence for a modulatory role of β-adrenoreceptors on methylphenidate-induced impulsive responding.