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

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.

Endogenous neurotensin is involved in estrous cycle related alterations in prepulse inhibition of the acoustic startle reflex in female rats

“…In the current study, there was a non-significant trend (p=0.06) for PPI in males to be greater than females. Previous studies in rodents report either no difference in PPI between males and females (Bubeníková et al, 2005;Plappert et al, 2005;Swerdlow et al, 1993) or PPI in males greater than females (Melnick et al, 2002). Conflicting results are most likely due to the unknown estrous cycle stage of female rats at the time of testing (e.g.…”

“…Habituation was analyzed by comparison of average startle amplitudes in pulse alone startle trials #1-4 compared to trials #5-11. Because a large degree of habituation to the pulse alone startle occurs in the initial pulse alone trials, it is common practice to disregard the initial pulse alone trials in computation of PPI (Bubeníková et al, 2005;Gogos and Van den Buuse, 2004;Koch, 1998;Plappert et al, 2005;Swerdlow et al, 2000;Vaillancourt et al, 2002). Percent PPI was calculated and analyzed using the average amplitude of pulse alone trials #5-11 using the formula: %PPI= 100− (prepulse/pulse startle amplitude × 100/pulse alone startle amplitude of trials #5-11).…”

“…Results from rodent studies investigating sex, estrous cycle and ovarian hormone regulation of PPI are less consistent (Bubeníková et al, 2005;Gogos and Van den Buuse, 2004;Gulinello et al, 2003;Koch, 1998;Plappert et al, 2005;Rupprecht et al, 1999;Vaillancourt et al, 2002;Van den Buuse and Eikelis, 2001). One explanation for the varied results of PPI studies in female rats is the significant intra-day variation in hormone levels across the female rats' 4-5 day estrous cycle (Gorski et al, 1975) ( figure 1A).…”

A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

“…Prepulse inhibition was inhibited by MDMA (2.5, 5, or 10 mg/kg) in males and females in the diestrous and metestous phase of their estrous cycle. However, females in proestorus and diestrous showed no disruption in sensorimotor gating to MDMA [15]. Catechol-0-methyltransferase (COMT) is responsible for several methylation reactions in the metabolism of MDMA [37] and, perhaps not coincidently, this ubiquitous enzyme has also been reported to be less active in women [97].…”

“…Many (11.7%) high school seniors in 2001 had tried ecstasy in the United States [67]. According to a 2005 report, 8-9% of teenagers (aged [15][16] in some schools in Ireland, the United Kingdom, and the Netherlands had taken ecstasy [44]. A national survey in Australia conducted in 2001 revealed that 5% of teenagers and 10% of young adults had used ecstasy at least once in the preceding year [40].…”