Analysis of neurotransmitter levels in addiction-related brain regions during synthetic cathinone self-administration in male Sprague-Dawley rats

Abstract

Rationale: Synthetic cathinones are used as stimulants of abuse. Different stimulants may induce distinct rates of disease progression, yielding neurochemical changes that may vary across brain regions or neurotransmitter systems. Objectives: This research sought to behaviorally and chemically differentiate stages of synthetic cathinone abuse through rodent self-administration and measurement of the neurotransmitter profile in multiple brain regions. Methods: Male rats were trained to self-administer α-PVP, mephedrone (4MMC), or saline. Half of each drug group stopped self-administering after autoshaping; the other half self-administered for another 21 days. Brain tissue from amygdala, hippocampus, hypothalamus, PFC, striatum, and thalamus was profiled with electrochemical detection to assess neurotransmitter levels. Results: During autoshaping, the majority of infusions were delivered noncontingently. In the self-administration phase, rats responded more for α-PVP and 4MMC than for saline, demonstrating that both synthetic cathinones were reinforcing. Longer durations of exposure elevated 5-HIAA in hypothalamus, PFC, and hippocampus, indicating that learning may produce changes in addiction-related brain regions. Both synthetic cathinones decreased norepinephrine in hippocampus, while α-PVP decreased glutamate in hippocampus and PFC, and 4MMC decreased glutamate in thalamus. Furthermore, α-PVP increased dopaminergic metabolites in striatum, whereas 4MMC decreased serotonin in the amygdala, hippocampus, and PFC. Interestingly, neither synthetic cathinone affected dopamine levels despite their functional effects on the dopaminergic system. Conclusions: In summary, the neurotransmitter changes observed here suggest that synthetic cathinone use likely produces sequential neurochemical changes during the transition from use to abuse. Consequently, treatment need may differ depending on the progression of synthetic cathinone abuse.