Sex Differences in Abuse-Related Neurochemical and Behavioral Effects of 3,4-methylenedioxymethamphetamine (MDMA) in Rats
Matthew F. Lazenka, J. Suyama, Clayton T. Bauer, Matthew L. Banks, S. Negus
Pharmacology, Biochemistry, and Behavior August 24, 2016 DOI: 10.1016/j.pbb.2016.08.004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Female and male Sprague-Dawley rats |
| Intervention | MDMA |
| Dose | 0.32–3.2 mg/kg for ICSS; 1.0–3.2 mg/kg for microdialysis |
| Duration | ICSS: 10 min pretreatment (potency) and 10–180 min pretreatment (time course); microdialysis: 0–180 min |
| Measures | intracranial self-stimulation (ICSS), in vivo microdialysis |
| Topics | MDMA |
| Key findings | MDMA produced qualitatively similar effects on intracranial self-stimulation and nucleus accumbens dopamine and serotonin in both sexes, but the duration and peak of ICSS facilitation and dopamine increases were greater in females, and MDMA was more potent at increasing serotonin in females. The authors state these results provide evidence for heightened sensitivity of females to abuse-related behavioral and neurochemical effects of MDMA in rats. |
Abstract
ABSTRACT 3,4‐Methylenedioxymethamphetamine (MDMA) is a substrate for dopamine (DA), norepinephrine and serotonin (5HT) transporters that produces greater pharmacological effects on certain endpoints in females than males in both clinical and rodent preclinical studies. To evaluate potential for sex differences in abuse‐related MDMA effects, the present study compared MDMA effects on intracranial self‐stimulation (ICSS) and on in vivo microdialysis measurements of DA or 5HT in the nucleus accumbens (NAc) in female and male Sprague‐Dawley rats. For ICSS studies, electrodes were implanted in the medial forebrain bundle and rats trained to press for electrical stimulation over a range of frequencies (56–158 Hz, 0.05 log increments) under a fixed‐ratio 1 schedule, and the potency (0.32–3.2 mg/kg, 10 min pretreatment) and time course (3.2. mg/kg, 10–180 min pretreatment) of MDMA effects were determined. For in vivo microdialysis, rats were implanted with bilateral guide cannulae targeting the NAc, and the time course of MDMA effects (1.0–3.2 mg/kg, 0–180 min) on DA and 5HT was determined. MDMA produced qualitatively similar effects in both sexes on ICSS (both increases in low ICSS rates maintained by low brain‐stimulation frequencies and decreases in high ICSS rates maintained by high brain‐stimulation frequencies) and microdialysis (increases in both DA and 5HT). The duration and peak levels of both abuse‐related ICSS facilitation and increases in NAc DA were longer in females. MDMA was also more potent to increase 5HT in females. These results provide evidence for heightened sensitivity of females to abuse‐related behavioral and neurochemical effects of MDMA in rats. HighlightsTime course of 3.2 mg/kg MDMA rate‐increasing effects in ICSS greater in femalesMDMA more potent to increase serotonin in nucleus accumbens of females3.2 mg/kg MDMA produces greater DA increases in nucleus accumbens of females.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- Balancing Therapeutic Efficacy and Safety of MDMA and Novel MDXX Analogues as Novel Treatments for Autism Spectrum Disorder. Psychedelic Medicine September 1, 2023
- Does MDMA have treatment potential in sexual dysfunction? A systematic review of outcomes across the female and male sexual response cycles. Sexual medicine reviews December 23, 2023
- A Multimodal Preclinical Assessment of MDMA in Female and Male Rats: Prohedonic, Cognition Disruptive, and Prosocial Effects. Psychedelic Medicine June 1, 2024
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Cites 16
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- Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”): The Influence of Gender and Genetics (CYP2D6, COMT, 5-HTT) PLoS One October 24, 2012
- Relation of sex and estrous phase to deficits in prepulse inhibition of the startle response induced by ecstasy (MDMA) Behavioural Pharmacology March 1, 2005
- Intravenous self-administration of entactogen-class stimulants in male rats. Neuropharmacology December 2015
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