Effects of methiopropamine on cognitive function and monoaminergic systems in mice
Mohd Khairulanwar Bunaim1,2, Nor Syafinaz Yaakob1, Hanafi Ahmad Damanhuri3
1Faculty of Pharmacy, Centre for Drug and Herbal Development, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Abstract:
Methiopropamine (MPA), a novel psychoactive substance (NPS) similar to methamphetamine (METH), warrants investigation into its neurotoxic effects on cognitive function and behaviors due to limited existing research. Therefore, this study aimed to explore the effects of MPA on several behavioral parameters in mice, brain levels of monoamine neurotransmitters, and p-ERK1/2 expression. Mice were randomly divided into four groups (n = 10) which received daily intraperitoneal injections of either saline, 1 or 3 mg/kg of MPA, or 1 mg/kg of METH for 7 days. The novel object recognition test (NORT) revealed a significant decline in recognition memory, particularly evident at a dose of 3 mg/kg of MPA, similar to METH at 1 mg/kg, observed 24 h post-withdrawal. MPA at 3 mg/kg also impaired working and reference memory performance in the 8-arm radial maze (8-ARM) test and exhibited an anxiolytic effect in the open field test (OFT). These cognitive impairments were accompanied by decreased dopaminergic parameters and p-ERK1/2 expression within the prefrontal cortex (PFC). This further suggests that MPA neurotoxicity is targeted at the dopaminergic transmission in the PFC. In conclusion, MPA consumption is associated with memory impairment, which is attributable to dopaminergic deficits and reduced p-ERK1/2 activities in the PFC.
Insights
Methiopropamine (MPA) impairs memory and working abilities in mice, similar to methamphetamine. These effects are linked to reduced dopamine and p-ERK1/2 in the prefrontal cortex, indicating MPA neurotoxicity.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Novel psychoactive substances (NPS) like methiopropamine (MPA) require neurotoxicity research.
- Methiopropamine (MPA) shares structural similarities with methamphetamine (METH).
Purpose of the Study:
- To investigate MPA's neurotoxic effects on mouse behavior.
- To analyze MPA's impact on neurotransmitter levels and p-ERK1/2 expression in the brain.
Main Methods:
- Mice received daily intraperitoneal injections of saline, MPA (1 or 3 mg/kg), or METH (1 mg/kg) for 7 days.
- Behavioral tests included novel object recognition (NORT), 8-arm radial maze (8-ARM), and open field test (OFT).
- Brain monoamine neurotransmitter levels and p-ERK1/2 expression in the prefrontal cortex (PFC) were measured.
Main Results:
- MPA (3 mg/kg) significantly impaired recognition memory in NORT, comparable to METH (1 mg/kg).
- MPA (3 mg/kg) also reduced working and reference memory in the 8-ARM test and showed anxiolytic effects in the OFT.
- Cognitive deficits correlated with decreased dopaminergic parameters and p-ERK1/2 expression in the PFC.
Conclusions:
- MPA consumption leads to memory impairment in mice.
- MPA-induced neurotoxicity targets dopaminergic transmission in the prefrontal cortex.
- Reduced dopaminergic activity and p-ERK1/2 levels contribute to MPA's cognitive effects.
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