Effects of 3,4-Methylenedioxymethamphetamine Administration on Retinal Physiology in the Rat

Abstract

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known to produce euphoric states, but may also cause adverse consequences in humans, such as hyperthermia and neurocognitive deficits. Although MDMA consumption has been associated with visual problems, the effects of this recreational drug in retinal physiology have not been addressed hitherto. In this work, we evaluated the effect of a single MDMA administration in the rat electroretinogram (ERG). Wistar rats were administered MDMA (15 mg/kg) or saline and ERGs were recorded before (Baseline ERG), and 3 h, 24 h, and 7 days after treatment. A high temperature (HT) saline-treated control group was also included. Overall, significantly augmented and shorter latency ERG responses were found in MDMA and HT groups 3 h after treatment when compared to Baseline. Twenty-four hours after treatment some of the alterations found at 3 h, mainly characterized by shorter latency, tended to return to Baseline values. However, MDMA-treated animals still presented increased scotopic a-wave and b-wave amplitudes compared to Baseline ERGs, which were independent of temperature elevation though the latter might underlie the acute ERG alterations observed 3 h after MDMA administration. Seven days after MDMA administration recovery from these effects had occurred. The effects seem to stem from specific changes observed at the a-wave level, which indicates that MDMA affects subacutely (at 24 h) retinal physiology at the outer retinal (photoreceptor/bipolar) layers. In conclusion, we have found direct evidence that MDMA causes subacute enhancement of the outer retinal responses (most prominent in the a-wave), though ERG alterations resume within one week. These changes in photoreceptor/bipolar cell physiology may have implications for the understanding of the subacute visual manifestations induced by MDMA in humans.

Attention-Deficit/Hyperactivity Disorder Animal Model Presents Retinal Alterations and Methylphenidate Has a Differential Effect in ADHD versus Control Conditions

“…The flicker 1st ( Figure 2 D) and 2nd ( Figure 2 E) harmonic responses, which are thought to be the most representative of the original waveform [ 24 ], were also analyzed to assess the function of cones. The ADHD model presented a significant increase in the 1st (12.7 ± 1.5 µV) and 2nd (9.9 ± 1.1 µV) harmonic amplitude in comparison with the controls (9.4 ± 1.1 and 5.7 ± 0.5 µV, respectively).…”

“…ERG recordings were performed after overnight dark adaptation to evaluate retinal physiology using corneal gold wire electrodes as previously described by our group [ 24 , 25 ]. Under dim red light (λ > 600 nm), animals were anesthetized by an intraperitoneal injection with ketamine (90 mg/kg; Nimatek, Dechra, Northwich, UK) and xylazine (10 mg/kg; Sedaxylan, Dechra, Northwich, UK).…”

Caffeine, Nicotine and MDMA Effects on Retina suggestive of Potential Functional Consequences

“…One of the few reports available, on human, reported that retinal nerve fibre layer (RNFL) thinning was associated with chronic alcohol and tobacco use [20]. MDMA was also reported to have influence on retina physiology in rats [21]. Another research during which experimental mice were administered nicotine reported that nicotine altered retinal pigment epithelial cells morphology and function, caused thinning of the outer nuclear layer and a damaged photoreceptor-RPE interface in manners that pointed to possible pathological effects of nicotine on retina [22] Furthermore, there are reports that associated relative thinning of the retina with the chronic use of certain drugs including the hydroxychloroquine therapy in human subjects [23].…”