The acute effects of methamphetamine on synaptic plasticity in the CA1 region of the mouse hippocampus

Abstract

Monoamines affect LTP in the CA1 region of the hippocampus. GBR12935 and cocaine, both which increase the concentration of synaptic dopamine (DA), have been shown to increase LTP (Swant and Wagner 2006; Thompson et al. 2005). D1/D5 DA receptor agonists also increase LTP (Otmahkova and Lisman 1996; Stramiello and Wagner 2008). Methamphetamine (METH) application results in an increase in the concentration of extracellular monoamines. Here we study the acute effects of methamphetamine on LTP in the CA1 region of the mouse hippocampus. In contrast to cocaine, 1 and 10 microM METH application decreased LTP. The application of METH at a concentration of 30 microM resulted in a profound decrease in LTP, along with an increase in baseline synaptic transmission. Thapsigargin, verapamil, or DL‐APV did not block the effects of METH on baseline synaptic transmission and LTP. However, pretreatment with D1/D5 DA receptor antagonist SCH23390 (5 microM) eliminated the effects of METH both on baseline synaptic transmission and on LTP. These unexpected results show that unlike cocaine, which increases LTP in the CA1, METH decreases LTP through a process which requires activation of D1/D5 DA receptors.