Different doses of methamphetamine alter long-term potentiation, level of BDNF and neuronal apoptosis in the hippocampus of reinstated rats

Abstract

Methamphetamine (METH) is a psychostimulant. The precise mechanisms of its effects remain unknown and current relapse treatments have low efficacy. However, brain-derived neurotrophic factor (BDNF) and neuronal plasticity are essential contributors, despite paradoxical reports and a lack of comprehensive studies. Therefore, we investigated the effects of different doses of METH on long-term potentiation (LTP), BDNF expression and neuronal apoptosis in the hippocampus of reinstated rats. Rats were injected intraperitoneally with METH (1, 5, or 10 mg/kg) or saline, and trained in a conditioned place preference paradigm. Following implementation of the reinstatement model, electrophysiology, western blotting and TUNEL assay were performed to assess behavior, LTP components, BDNF expression, and neuronal apoptosis, respectively. The results demonstrated that the preference scores, population spike amplitude and BDNF expression markedly decreased in the METH (10 mg/kg) group compared with the other groups. In contrast, METH (5 mg/kg) significantly increased these factors more than the control group. There was no change in variables between METH (1 mg/kg) and the control group. Also, apoptosis of the hippocampus was increased in the METH (10 mg/kg) group compared with the METH (5 mg/kg) group. These results suggest that alterations in synaptic plasticity, expression of BDNF and neuronal apoptosis in the hippocampus has a vital role in the context-induced reinstatement of METH seeking.

Methamphetamine augments HIV-1 gp120 inhibition of synaptic transmission and plasticity in rat hippocampal slices: Implications for methamphetamine exacerbation of HIV-associated neurocognitive disorders

“…In this study we observed that gp120, when applied alone, attenuated hippocampal LTP, which is consistent with the findings that gp120 inhibited short- and long-term potentiation in the hippocampus when applied acutely onto the hippocampal slices ( Dong and Xiong, 2006 ; Shen et al, 2015 ), administered to the brain via intracerebroventricular infusion (for 3–5 days) ( Sanchez-Alavez et al, 2000 ), or overexpressed in the brain in gp120-transgenic animals ( Hoefer et al, 2015 ; Krucker et al, 1998 ). We also observed that Meth reduced LTP when applied acutely, which is in agreement with the results that Meth reduced LTP recorded either in the CA1 region of mouse hippocampus in vitro ( Swant et al, 2010 ) and rat hippocampus ex vivo ( Hori et al, 2010 ; Onaivi et al, 2002 ) or in the dentate gyrus in vivo in reinstated rats ( Shahidi et al, 2019 ), along with the findings observed in the medial portion of the prefrontal cortex ( Ishikawa et al, 2005 ) and in the cortical-striatal region of rats with self-administration of Meth ( Huang et al, 2017 ). In addition to its suppressive effect, Meth was also found, when administered for a long-term with a low dose, to enhance LTP in differentiating and mature mouse dentate gyrus neural cells ( Baptista et al, 2016 ).…”

Caveolin-1 Expression in the Dorsal Striatum Drives Methamphetamine Addiction-Like Behavior

“…Accumulating evidence indicates that addictive drugs hijack the striatal memory systems to produce the behavioral effects [ 24 ]. Accordingly, methamphetamine exposure has been shown to alter synaptic plasticity in multiple neuronal systems of the reward circuitry, including the striatum [ 15 , 48 , 49 , 50 , 51 , 52 , 53 ]. Synaptic adaptations in the dorsal striatum underlie habit learning [ 54 ] and escalation of methamphetamine self-administration-induced altered plasticity in the dorsal striatum might therefore play a role in enhancing vulnerability to methamphetamine addiction [ 19 ].…”

High-dose fluoxetine improved long-term potentiation of the hippocampal dentate gyrus in male rats

“…Therefore, fluoxetine treatment increased synaptic plasticity and dendritic spine remodeling induced the growth of cerebrocortical synapses (Rubio et al, 2013). LTP, as a form of synaptic plasticity, has been regarded as a critical cellular mechanism underlying learning and memory (Shahidi et al, 2019a).…”