Antagonism of 5‐HT2A receptors attenuates the effects of amphetamine and 3,4‐methylenedioxymethamphetamine on wakefulness and dopamine overflow
Kevin Sean Murnane, Leonard Lee Howell
The FASEB Journal April 1, 2012 DOI: 10.1096/fasebj.26.1_supplement.1040.4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Rhesus monkeys |
| Interventions | Amphetamine MDMA M100907 |
| Topics | MDMA Serotonin |
| Key findings | Amphetamine and MDMA dose-dependently increased wakefulness in rhesus monkeys, with amphetamine showing a more pronounced effect, possibly due to longer duration of action. Blocking 5-HT2A receptors with M100907 attenuated both the wake-promoting effects and dopamine overflow in the caudate nucleus. The authors suggest that increased dopamine neurotransmission may be necessary for the wake-promoting effects of amphetamines. |
Abstract
The neuropharmacology of the sleep and arousal systems involves a complex interplay between multiple neurotransmitter systems. Previous work has downplayed the role of dopamine in sleep and wakefulness, at least in part, because dopamine neurons do not appear to change their firing rates across arousal states. In the present study, we examined the wake promoting effects of amphetamine and 3,4‐methylenedioxymethamphetamine (MDMA) in rhesus monkeys using noninvasive telemetric monitoring. To evaluate the importance of dopamine, we used in vivo microdialysis targeting the caudate nucleus and pretreatment experiments with the selective 5‐HT2A receptor antagonist M100907. We targeted 5‐HT2A receptors because previous studies found that antagonizing this receptor attenuates some of the behavioral and neurochemical effects of amphetamine and MDMA. We found that amphetamine and MDMA significantly and dose‐dependently increased wakefulness. The effects of amphetamine were more pronounced than those of MDMA, but this may have been the result of different durations of action. Antagonism of 5‐HT2A receptors attenuated the effects of amphetamine and MDMA on both wakefulness and dopamine overflow. These findings suggest that increased dopamine neurotransmission may be necessary for the wake promoting effects of amphetamines. These studies were supported by USPHS grants (DA 00517 and RR 00165).
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.