Methylphenidate-induced impulsivity: pharmacological antagonism by beta-adrenoreceptor blockade.
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 beta-adrenoreceptor blocker, or prazosin, an alpha1-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 beta-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-D beta H saporin-induced cortical noradrenaline depletion on methylphenidate-induced impulsivity. Contrary to the effects of beta-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 beta-adrenoreceptors on methylphenidate-induced impulsive responding.
Milstein
J A
JA
Behavioural and Clinical Neuroscience Institute and Department of Experimental Psychology, University of Cambridge, Cambridge, UK.
Dalley
J W
JW
Robbins
T W
TW
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D007175:Impulsive Behavior / Q000139:chemically induced*; D008297:Male; D008774:Methylphenidate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology; D000076985:Saporins; D012702:Serotonin Antagonists / Q000494:pharmacology
D018674:Adrenergic Antagonists; D000911:Antibodies, Monoclonal; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D054789:Ribosome Inactivating Proteins, Type 1; D012702:Serotonin Antagonists; C101397:anti-dopamine beta-hydroxylase immunotoxin; D008774:Methylphenidate; D000076985:Saporins; D009638:Norepinephrine