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.
Tye
Kay M
KM
Ernest Gallo Clinic & Research Center, University of California, San Francisco, Emeryville, California, USA.
Tye
Lynne D
LD
Cone
Jackson J
JJ
Hekkelman
Evelien F
EF
Janak
Patricia H
PH
Bonci
Antonello
A
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D008774:Methylphenidate