Relation of sex and estrous phase to deficits in prepulse inhibition of the startle response induced by ecstasy (MDMA)

MDMA (ecstasy) dose-dependently reduces prepulse inhibition (PPI), a measure of sensorimotor gating, in both male and female Wistar rats. Male rats show a greater increase in the acoustic startle response (ASR) than females after MDMA. Among females, sensitivity to MDMA’s PPI-disrupting effect varies across the estrous cycle: rats in diestrous and metestrous phases exhibit larger PPI deficits, while those in proestrous and estrous phases are less affected.

Study at a glance

Abstract

Sensorimotor gating is the ability of a weak sensory event to inhibit the motor response to an intense stimulus. Drugs that act as serotonin releasers, such as MDMA (3,4-methylenedioxymethamphetamine), impair sensorimotor gating, which is measured as a prepulse inhibition (PPI) of the acoustic startle response. The first objective of the present study was to compare the effect of different doses of MDMA on PPI and the acoustic startle response (ASR) in male and female Wistar rats. The second objective was to examine the effect of MDMA on PPI across the estrous cycle in female rats. MDMA was administered in doses of 2.5, 5 and 10 mg/kg s.c. 15 min before the start of the experiment. The controls received saline in equivalent volumes. MDMA dose-dependently decreased PPI in both the male and female rats and produced higher levels of ASR in the male rats compared to the females. In addition, we found that female rats in the diestrous and metestrous phases are more sensitive to MDMA and showed higher deficits in PPI than female rats in the proestrous and estrous phases. Our result showed that female rats in the proestrous and estrous phases were less sensitive to the disruption of PPI by MDMA.