Neurotoxic Effects of Methamphetamine on Rat Hippocampus Pyramidal Neurons

Abstract

Methamphetamine (MAP) is known to alter behavior and cause deficits in learning and memory. While the major site of action of MAP is on mesolimbic dopaminergic pathways, the effects on learning and memory raise the possibility of important actions in the hippocampus. We have studied electrophysiologic and morphologic effects of MAP in the CA1 region of hippocampus from young male rats chronically exposed to MAP, male rats exposed during gestation only and the effects of bath perfusion of MAP onto brain slices from control rats. Pyramidal neurons in brain slices from chronically exposed rats had reduced membrane potential and membrane resistance. Long-term potentiation (LTP) was reduced as compared to control, but when MAP was acutely perfused over control slices the amplitude of LTP was increased. LTP in young adult animals that had been gestationally exposed to MAP showed reduced LTP as compared to controls. Morphologically CA1 pyramidal neurons in chronically exposed animals showed a high prevalence of extensive blebbing of dendrites. We conclude that the NMDA receptor and the process of LTP are also targets of MAP dysfunction, at least in the hippocampus.

Functional changes in piriform cortex pyramidal neurons in the chronic methamphetamine-treated rat

“…Similar morphological changes were also seen in our previous study on CA1 pyramidal cells in MAP-treated rats (Hori et al 2010). The membrane potential and input resistance in MAP-treated rat neurons significantly decreased as compared to control neurons.…”

“…LTP is an electrophysiological response that is widely used to measure synaptic plasticity following high-frequency stimulation, and is a key event in the early steps of some forms of memory formation (Lynch 2004). Chronic MAP-treatment affects the formation of LTP in rodent hippocampal slices (Hori et al 2010;Swant et al 2010) and the present experiments show that LTP in piriform cortex pyramidal neurons in response to lateral olfactory tract stimulation is also impaired by chronic MAP. The reduced response to NMDA receptors and the altered voltage-dependence of the NMDA response may render this receptor unable to effectively induce this NMDA-dependent LTP (Kanter and Haberly 1990).…”

“…The present study extends these studies on the electrophysiological and morphological effects of chronic MAP to the pyramidal neurons of the rat piriform cortex, a region that receives fibers directly from the olfactory bulb and has a well-defined neuronal architecture, similar to that in the hippocampus (Hori et al 2010). Coupled with the defined role of the piriform cortex in olfactory processing and learning, the piriform cortex is also a suitable region for the study of synaptic plasticity (Linster and Hasselmo 2001).…”

“…Lucifer yellow was injected electrophoretically via a glass microelectrode, and the slice was subsequently fixed it in 4% para-formaldehyde. Neurons were observed under a fluorescence microscope, with images digitized and stored on hard disk, as in our previous papers (Hori et al 2001(Hori et al , 2002(Hori et al , 2010. a.…”

“…MAP-induced sensitization and neurotoxicity, for example, can be blocked by NMDA receptor antagonists (Ohmori et al 1994; Thomas and Kuhn, 2005). The physiological mechanisms underlying the disability of memory and learning with chronic MAP treatment have largely focused on the rat hippocampus (Ohmori et al 1994;Hori et al 2010;Han et al 2012) and neostriatum (Moriguchi et al 2002). Activation of NMDA receptors in rat hippocampal slices mediates long-term potentiation (LTP) at Schaffer collateral to CA1 neuron synapses (Hori et al 2010;Swant et al 2010), and this form of synaptic plasticity is believed to be an important aspect of the early stages of the formation of some types of memory (Lynch 2004).…”