Drugs used in the treatment of attention-deficit/hyperactivity disorder affect postsynaptic firing rate and oscillation without preferential dopamineautoreceptor action

Background: Current theories propose that low doses of catecholaminergic st imulants reduce symptoms in patients with attention-deficient/hyperactivity disorder by acting on autoreceptors to reduce catecholaminergic transmissi on; few data are available that directly address this hypothesis. Methods: We investigated the autoreceptor and postsynaptic receptor actions of systematically administered stimulants on dopaminergic systems in rats with single-unit recording in the substantia nigra pars compacta and globus pallidus, respectively. Results: Dose-response curves for rate indicated that the potencies of the indirect-acting agonists methylphenidate and D-amphetamine at dopaminergic autoreceptors were not greater than at postsynaptic receptors; in fact, D-a mphetamine was more potent postsynaptically. In addition to effects on firi ng rate, spectral/wavelet analyses indicated that these drugs had prominent effects on postsynaptic multisecond oscillations. These oscillations were shifted by stimulants from baseline periods of similar to 30 sec to periods of 5-10 sec. Effects on pattern were found at doses as low as 1.0 mg/kg (m ethylphanidate) and 0.2 mg/kg (D-amphetamine). At this latter dose, D-amphe tamine had little effect presynaptically. Conclusions: These are prior results demonstrate that there is no autorecep tor-preferring dose range of catecholaminergic stimulants; these drugs at l ow doses are unlikely to reduce motor activity by this mechanism. Nonethele ss, they might affect attentive and cognitive processes by modulating multi second temporal patterns of central activity. (C) 2001 Society of Biologica l Psychiatry.