Exposure to 3,4‐methylenedioxymethamphetamine (MDMA) on postnatal days 11–20 induces reference but not working memory deficits in the Morris water maze in rats: implications of prior learning

Abstract

3,4-methylenedioxymethamphetamine (MDMA) in previous experiments has been shown to induce long-term spatial and sequential learning and memory deficits in adult offspring after exposure to the drug on postnatal (P) days 11-20, but not after exposure on P1-10. Herein we further tested for the effects of MDMA (0, 5, 10 or 20 mg/kg x 2/day) after exposure on P11-20 on reference and working memory in the Morris water maze (MWM), on reference memory in the Barnes maze, and on cued learning in the visible platform version of the MWM. The MWM and Barnes mazes were counterbalanced such that half the litters received the MWM-first and the other half received the Barnes maze first. Effects on MWM performance as a function of test order were observed. For animals that received the Barnes maze first, spatial MWM learning and memory trends were seen but they were not significantly different between MDMA groups and saline controls. For those receiving the MWM-first, there are consistent impairments on all measures in the MDMA groups compared to controls on MWM performance (latency, path length, and cumulative distance from the goal). On probe trials, MDMA animals receiving the MWM-first showed increased distance from the target site compared to controls. There were no MDMA effects seen on cued trials in the MWM or on straight channel swimming trials regardless of test order, indicating that MDMA had no effects on swimming ability or on the skills needed to learn the MWM. Similarly, there were no effects of MDMA on MWM working memory regardless of test order. No MDMA effects on the Barnes maze were found regardless of test order, however, the interpretation of this finding was compromised by the poor performance of the animals on this task.

Treatment with MDMA from P11–20 disrupts spatial learning and path integration learning in adolescent rats but only spatial learning in older rats

“…For example, all animals performed similarly in straight channel swimming, a measure that was previously shown to uncover motor deficits in offspring exposed to valproic acid (Vorhees 1987a). Offspring exposed to MDMA were also shown not to be affected in the visible platform phase of the MWM (Broening et al 2001;Vorhees et al 2004;Williams et al 2005), which further supports that MDMA does not induce deficits to sensorimotor systems. The weight differences seen in the pups during dosing do not appear to be due to the inability of the animals to nurse, as large litter control groups that simulate comparable degrees of undernutrition to that induced by MDMA do not show learning and memory deficits as do the MDMA-treated offspring (Williams et al 2003).…”

“…We have previously shown that MDMA treatment from P11-20 causes spatial and path integration learning and memory deficits when the animals are tested at P60 (Broening et al 2001;Williams et al 2003;Vorhees et al 2004) and at approximately P90 (Cohen et al 2005). The purpose of this study was to further elucidate the behavioral effects of MDMA by testing younger (P30 and P40) and older (P180 and P360) rats in the MWM and CWM.…”

“…This sex difference is likely due to the activational effects of gonadal steroids because the P30 and P40 animals were tested before puberty or during the transition from puberty to adulthood. Therefore, the incomplete maturation of the gonadal hormones may prevent the sexually dimorphic effects seen in young-adult and older animals (tested after P60) (Broening et al 2001;Williams et al 2003;Vorhees et al 2004). Slight weight differences were seen in the younger animals; however, these did not appear to affect the motor performance of MDMAtreated animals.…”

“…Exposure to MDMA from P11-20 in rats induces spatial and path integration learning and memory deficits when the animals are tested during adulthood; however exposure from P1-10 induces no deficits in either learning paradigm (Broening et al 2001). In the Morris water maze (MWM), MDMA-treated animals show increased latencies, path lengths, and cumulative distances from the platform during acquisition, reversal (where the platform is moved to the opposite quadrant), and reduced platform (the platform is reduced from 10 × 10 cm to 5 × 5 cm and moved to the original quadrant) phases of hidden platform training (Broening et al 2001;Williams et al 2003;Vorhees et al 2004;Cohen et al 2005). During probe (memory) trials, MDMA-treated animals had a greater average distance from the platform than saline (SAL)-treated animals.…”

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

“…The following sections will provide a brief historical perspective on this drug and then contrast the pharmacokinetics and pharmacodynamics of MDMA at prenatal, adolescent, and adult ages using measures where comparative information is available. In addition, although epidemiological evidence indicates that infants are infrequently exposed to MDMA, some laboratories consider the preweanling rat to be analogous to third trimester human [160]. Therefore, evidence from this period of drug treatment will also be described as the goal of this paper is to describe whether there are age differences in MDMA responsivity, and, when present, to identify the mechanisms mediating the variability in vulnerability across the lifespan.…”