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Methamphetamine and the Synthetic Cathinone 3,4-Methylenedioxypyrovalerone (MDPV) Produce Persistent Effects on
Erin K Nagy1, Paula F Overby1, Jonna M Leyrer-Jackson2
1Department of Psychology, Behavioral Neuroscience and Comparative Psychology Area, Arizona State University, Tempe, AZ 85287, USA.
Abstract:
Psychostimulants alter cellular morphology and activate neuroimmune signaling in a number of brain regions, yet few prior studies have investigated their persistence beyond acute abstinence or following high levels of voluntary drug intake. In this study, we examined the effects of the repeated binge-like self-administration (96 h/week for 3 weeks) of methamphetamine (METH) and 21 days of abstinence in female and male rats on changes in cell density, morphology, and cytokine levels in two addiction-related brain regions-the prefrontal cortex (PFC) and dorsal striatum (DStr). We also examined the effects of similar patterns of intake of the cocaine-like synthetic cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV) or saline as a control. Robust levels of METH and MDPV intake (~500-1000 infusions per 96 h period) were observed in both sexes. We observed no changes in astrocyte or neuron density in either region, but decreases in dendritic spine densities were observed in PFC pyramidal and DStr medium spiny neurons. The microglial cell density was decreased in the PFC of METH self-administering animals, accompanied by evidence of microglial apoptosis. Changes in microglial morphology (e.g., decreased territorial volume and ramification and increased cell soma volume) were also observed, indicative of an inflammatory-like state. Multiplex analyses of PFC and DStr cytokine content revealed elevated levels of various interleukins and chemokines only in METH self-administering animals, with region- and sex-dependent effects. Our findings suggest that voluntary binge-like METH or MDPV intake induces similar cellular perturbations in the brain, but they are divergent neuroimmune responses that persist beyond the initial abstinence phase.
Insights
Repeated methamphetamine (METH) and MDPV use alters brain cell structure and neuroinflammation, with changes persisting after abstinence. These psychostimulants impact dendritic spines and microglial cells in addiction-related brain regions.
Area of Science:
- Neuroscience
- Neuropharmacology
- Cellular Biology
Background:
- Psychostimulants can alter brain cell structure and neuroimmune responses.
- Few studies have examined the long-term effects of high voluntary psychostimulant intake and abstinence on brain changes.
Purpose of the Study:
- To investigate the persistent effects of binge-like methamphetamine (METH) and 3,4-methylenedioxypyrovalerone (MDPV) self-administration on cell density, morphology, and cytokine levels in the prefrontal cortex (PFC) and dorsal striatum (DStr).
- To compare these effects between sexes following a 21-day abstinence period.
Main Methods:
- Rats (male and female) underwent repeated binge-like self-administration of METH or MDPV (96 h/week for 3 weeks).
- Cell density, morphology, and cytokine levels in the PFC and DStr were analyzed after 21 days of abstinence.
- Control animals received saline.
Main Results:
- No changes in astrocyte or neuron density were observed.
- Decreased dendritic spine densities were found in PFC pyramidal and DStr medium spiny neurons.
- METH self-administration led to decreased microglial cell density in the PFC, with evidence of apoptosis and altered morphology indicative of inflammation.
- Elevated levels of interleukins and chemokines were detected in the PFC and DStr of METH-treated animals, showing region- and sex-dependent effects.
Conclusions:
- Voluntary binge-like intake of METH or MDPV induces persistent cellular changes in addiction-related brain regions.
- METH self-administration triggers divergent neuroimmune responses, including microglial alterations and elevated cytokine levels, that persist beyond acute abstinence.
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