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Repeated exposure to methylenedioxymethamphetamine (MDMA) alters nucleus accumbens neuronal responses to dopamine and
T Obradovic1, K M Imel, S R White
1Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164, USA.
Abstract:
The purpose of this experiment was to investigate the effects of repeated exposure to methylenedioxymethamphetamine (MDMA) on responses of neurons in the nucleus accumbens of anesthetized rats to microiontophoretically-applied dopamine and serotonin. In tests conducted 1-4 days or 9-15 days following the last injection of MDMA (20 mg/kg, s.c., twice daily for 4 days), the inhibitory effects of both dopamine and serotonin on glutamate-evoked firing of nucleus accumbens cells were significantly attenuated compared to effects in control rats that were pretreated with saline injections. The inhibitory effect of the D1 receptor agonist SKF38393 was also significantly attenuated in the MDMA-pretreated rats. In contrast, the amount of inhibition of glutamate-evoked firing produced by application of GABA did not significantly differ between the MDMA-pretreated and the saline-pretreated rats. The neurotoxicity of the MDMA treatment regimen was confirmed by demonstrating that 3H-paroxetine binding was significantly decreased in the medial prefrontal cortex and the nucleus accumbens of the MDMA-pretreated rats. The mechanisms that produce the attenuated inhibitory responses to dopamine and serotonin following repeated injections of MDMA are not known. However, the results of these experiments indicate that repeated MDMA administration induces long-lasting changes in dopaminergic as well as serotonergic neurotransmission in the nucleus accumbens.
Insights
Repeated methylenedioxymethamphetamine (MDMA) exposure significantly reduces the brain
Area of Science:
- Neuroscience
- Pharmacology
- Neurobiology
Background:
- Methylenedioxymethamphetamine (MDMA) is a psychoactive drug with known neurotoxic potential.
- The nucleus accumbens is a key brain region involved in reward and motivation, heavily influenced by dopamine and serotonin.
- Understanding MDMA's long-term effects on neurotransmission is crucial for assessing its impact on brain function.
Purpose of the Study:
- To investigate the long-term effects of repeated MDMA exposure on neuronal responses in the rat nucleus accumbens.
- To determine how MDMA affects dopamine and serotonin signaling within this brain region.
Main Methods:
- Rats were administered MDMA or saline repeatedly over four days.
- Neuronal responses to dopamine, serotonin, and GABA were measured in the nucleus accumbens using microiontophoresis.
- Neurotoxicity was assessed by measuring 3H-paroxetine binding in specific brain regions.
Main Results:
- Repeated MDMA exposure significantly attenuated the inhibitory effects of dopamine and serotonin on nucleus accumbens neurons.
- The inhibitory effect of a D1 receptor agonist was also reduced in MDMA-treated rats.
- MDMA treatment led to a significant decrease in 3H-paroxetine binding, indicating serotonergic neurotoxicity.
Conclusions:
- Repeated MDMA administration induces long-lasting alterations in dopaminergic and serotonergic neurotransmission in the nucleus accumbens.
- These findings suggest significant neuroadaptive changes in response to MDMA exposure.