Effects of methylphenidate on the inhibitory postsynaptic potential in rat locus coeruleus neurons

Effects of methylphenidate (MPH), an agent used clinically for the treatment of children presenting the attention-deficit/hyperactivity disorder (AD/HD), on synaptic transmission in the rat locus coeruleus (LC) were examined by intracellular recording methods. Bath-application of MPH (30 nM-3 microM) increased the amplitude of the inhibitory postsynaptic potential (IPSP), while it did not change the amplitude of the excitatory postsynaptic potential (EPSP). MPH increased the time-to-peak and the half-decay time of the IPSP in LC neurons. MPH increased the amplitude of spontaneous IPSP: individual spontaneous IPSPs merged one into the other so as to produce regular, long-lasting waves of hyperpolarization. Clonidine (10 nM), a selective agonist for alpha 2-adrenoceptors, depressed the IPSP without affecting the EPSP in LC neurons. The results suggest that MPH enhances inhibitory synaptic transmission in the rat LC by depressing the norepinephrine (NE) re-uptake system.