Prelimbic medial prefrontal cortex has bidirectional control over the expression of behavioral sensitization to 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) depending on the context of drug administration.
Jacob A. Plocinski, Kevin T. Ball
Neuroscience Letters June 4, 2022 DOI: 10.1016/j.neulet.2022.136710 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA Lidocaine Physiological saline |
| Dose | MDMA 5.0 mg/kg twice daily for 5 days (induction); MDMA 2.5 mg/kg (challenge); lidocaine 100 μg/0.5 μl/side; physiological saline 0.5 μl/side |
| Duration | 5-day treatment period; challenge at approximately 2 weeks of withdrawal |
| Topics | MDMA |
| Key findings | Inactivating the prelimbic prefrontal cortex with lidocaine decreased MDMA challenge-induced locomotion in rats previously given MDMA in the test context but increased it in rats given MDMA in a different (home cage) context; no effect occurred in saline-pretreated rats. The authors propose that PL bidirectionally controls expression of locomotor sensitization to MDMA depending on the context of prior drug administration. |
Abstract
Behavioral sensitization to MDMA is observed in the vast majority of rats if tested in the same environment in which previous MDMA exposure occurred, but not if tested in a novel, unpaired context. Previous studies have revealed a critical role for the prelimbic region of medial prefrontal cortex (PL) in the expression of sensitization to MDMA, but these studies assessed sensitization only in MDMA-paired environments. Given that PL activity can both facilitate and suppress behavior depending on context, we tested the hypothesis that PL has bidirectional control over the expression of locomotor sensitization to MDMA depending on the context of drug administration. Rats were treated with either saline or MDMA (5.0 mg/kg) twice daily for 5 days, in either their home cages (unpaired groups) or the activity monitors that were used for tests of sensitization on challenge days (paired groups). Prior to MDMA challenge injections (2.5 mg/kg; at ∼2 weeks of withdrawal), rats received bilateral PL microinjections of either lidocaine (100 μg/0.5 μl/side) or physiological saline (0.5 μl/side). Locomotor activity in response to MDMA challenge was unaffected by PL inactivation in saline pretreated rats. However, PL inactivation caused a decrease in locomotion to the challenge injection in MDMA/paired rats and an increase in locomotion in MDMA/unpaired rats. These results establish a novel role for PL in suppressing the expression of behavioral sensitization when subjects are challenged in a drug-unpaired context, adding to the literature implicating PL activity in both the expression and inhibition of other drug-related behaviors.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 9
- MDMA‐Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta‐Analysis The Journal of Clinical Pharmacology October 28, 2021
- Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse Journal of Neurochemistry March 12, 2021
- Context‐dependent behavioural and neuronal sensitization in striatum to MDMA (ecstasy) administration in rats European Journal of Neuroscience July 1, 2006
- Differential involvement of prelimbic and infralimbic medial prefrontal cortex in discrete cue-induced reinstatement of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats. Psychopharmacology December 1, 2012
- Electrophysiological and structural alterations in striatum associated with behavioral sensitization to (±)3,4-methylenedioxymethamphetamine (Ecstasy) in rats: role of drug context. Neuroscience September 25, 2010
and 4 more in the library