Methylphenidate facilitates learning-induced amygdala plasticity

Although methylphenidate (Ritalin) has been used therapeutically for nearly 60 years, the mechanisms by which it acutely modifies behavioral performance are poorly understood. Here we combined intra–lateral amygdala in vivo pharmacology and ex vivo electrophysiology to show that acute administration of methylphenidate, as well as a selective dopamine transporter inhibitor, facilitated learning-induced strengthening of cortico-amygdala synapses through a postsynaptic increase in AMPA receptor–mediated currents, relative to those in saline-treated rats. Furthermore, local administration of methylphenidate in the lateral amygdala enhanced cue-reward learning through dopamine D1 receptor–dependent mechanisms and suppressed task-irrelevant behavior through D2 receptor–dependent mechanisms. These findings reveal critical and distinct roles for dopamine receptor subtypes in mediating methylphenidate-induced enhancements of neural transmission and learning performance.