Abstract
Methamphetamine (METH) is an addictive psychostimulant whose societal impact is on the rise. Emerging evidence suggests that psychostimulants alter synaptic plasticity in the brain—which may partly account for their adverse effects. While it is known that METH increases the extracellular concentration of monoamines dopamine, serotonin, and norepinephrine, it is not clear how METH alters glutamatergic transmission. Within this context, the aim of the present study was to investigate the effects of acute and systemic METH on basal synaptic transmission and long-term potentiation (LTP; an activity-induced increase in synaptic efficacy) in CA1 sub-field in the hippocampus. Both the acute ex vivo application of METH to hippocampal slices and systemic administration of METH decreased LTP. Interestingly, the acute ex vivo application of METH at a concentration of 30 or 60 µM increased baseline synaptic transmission as well as decreased LTP. Pretreatment with eticlopride (D2-like receptor antagonist) did not alter the effects of METH on synaptic transmission or LTP. In contrast, pretreatment with D1/D5 dopamine receptor antagonist SCH23390 or 5-HT1A receptor antagonist NAN-190 abrogated the effect of METH on synaptic transmission. Furthermore, METH did not increase baseline synaptic transmission in D1 dopamine receptor haploinsufficient mice. Our findings suggest that METH affects excitatory synaptic transmission via activation of dopamine and serotonin receptor systems in the hippocampus. This modulation may contribute to synaptic maladaption induced by METH addiction and/or METH-mediated cognitive dysfunction.
Highlights
Methamphetamine (METH) is one of the most addictive drugs in existence
After establishing field excitatory post-synaptic potentials (fEPSPs), we examined the effects of acute METH application on long-term potentiation (LTP)
Since METH increases the concentration of extracellular dopamine, serotonin, and norepinephrine [8], we considered the likelihood that METH’s effects on baseline synaptic transmission and/or LTP could be mediated via these receptor systems
Summary
Methamphetamine (METH) is one of the most addictive drugs in existence. METH can be prescribed (to be taken PO, by mouth) to treat ADHD and obesity, drug abusers administer much larger doses [3], through faster administration routes than those used clinically. Sixty-five percent of those admitted for METH/ amphetamine abuse reported smoking as the route of administration, eighteen percent reported injection, and 11 percent reported inhalation, [2]. The neural mechanisms that underlie these behavioral responses are not completely known. Lack of such knowledge impedes evidence-based development of pharmacological intervention to treat addiction, and to reverse damage caused by methamphetamine use
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