MDMA alone affects sensorimotor and prepulse inhibition responses in mice and rats: tips in the debate on potential MDMA unsafety in human activity

Abstract

Purpose MDMA is a psychoactive drug that has been increasingly abused worldwide, due to its entactogenic properties. However, concerns on its safety exist, particularly regarding its effects on attentional skills and performance. Evidence from the literature shows contrasting effects of MDMA. It generally acts as a pshychomotor stimulant, thus improving arousal and psychomotor function. However, MDMA has been demonstrated to negatively influence other skills. Consequently, human activities that require alertness, and accurate and quick reflexes (i.e. driving, operations at the workplace, etc.) could be negatively affected. In the present study, the effect of MDMA (0.1-20 mg/kg, intraperitoneally) on sensorimotor and startle/ prepulse inhibition responses was evaluated in a controlled rodent experimental setting. Methods Sensorimotor studies, evaluation of visual, acoustic, and tactile responses, evaluation of spontaneous locomotion, startle and repulse inhibition analyses were performed in an experimental controlled rodent model (rats and mice), following the administration of MDMA (0.1-20 mg/kg) intraperitoneally. Results Our findings show that all the MDMA-treated animals had impaired sensorimotor and prepulse inhibition responses compared to the control subjects at the early (5, 30 and 60 min) testing time points while all the effects disappeared, respectively, 6, 16 and 24 h post-MDMA treatment. Conclusions Within the ongoing debate on the safety of recreational abuse of MDMA, our results reveal acute prominent changes in sensorimotor and attentional performance, sensor response to external stimuli, and locomotor activity due to a single administration of a dose of MDMA (corresponding to a dose producing in humans both 'desirable' entactogenic effects and physiological adverse effects).

Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe

“…The differential effects of 25I-NBOMe were investigated using a battery of behavioral tests widely used in studies of "safetypharmacology" for the preclinical characterization of NPS in rodents (De Luca et al, 2015;Vigolo et al, 2015;Ossato et al, 2015;Ossato et al, 2016;Canazza et al, 2016;Canazza et al, 2017;Giannotti et al, 2017;Fantinati et al, 2017;Marti et al, 2019). To reduce the animal's stress induced by manipulation, and to confirm the stability and reproducibility over time of the responses of our tests, animals were trained two times per week for 2 weeks before the pharmacological treatment.…”

“…Visual response was verified by two behavioral tests, which evaluated the ability of the rat to capture visual information even when the animal is stationary (the visual object response) or when it is moving (the visual placing response). Visual object response test was used to assess the ability of the rat to see an object approaching from the front or side that causes the animal to move or turn the head or withdraw it (Marti et al, 2019). For the frontal visual response, a white horizontal bar was moved frontally to the rat head and the maneuver was repeated three times.…”

“…Evaluation of the visual object response was measured at 0, 5, 30, and 60 min post-injection. Visual placing response test is performed using a tail suspension modified apparatus able to bring down the rat towards the floor at a constant speed of 10 cm/s (Marti et al, 2019). A camera videotapes the downward movement of the rat.…”

“…Acoustic response measures the reflex of the rat in replay to an acoustic stimulus produced behind the animal. In particular, four acoustic stimuli of different intensities and frequencies were tested (Marti et al, 2019). Each sound test was repeated three times, giving a value of 1 if there was a response and 0 if not present, for a total score of 3 for each sound.…”

“…Moreover, several behavioral tests were performed to assess sensorimotor impairment as well as the risk of developing hyperthermia and have an altered nociceptive response under the effect of 25I-NBOMe. Additionally, due to the possibility to develop drug use-related psychotic disorders, we included an analysis of the acoustic startle reflex (prepulse inhibition, PPI) that is considered a marker of vulnerability for neuropsychiatric disorders (Siegel et al, 2013;Marti et al, 2019). Moreover, sex differences in drug addiction behavior have been extensively reported in both humans and rodents (Becker et al, 1982;Jackson et al, 2006;Zhao and Becker, 2010;Cummings et al, 2014;Fattore et al, 2014).…”