Comparison of the developmental effects of 5-methoxy-N,N-diisopropyltryptamine (Foxy) to (+/-)-3,4-methylenedioxymethamphetamine (ecstasy) in rats

Abstract

Rationale: We have previously shown that (+/-)-3,4-methylenedioxymethamphetamine (MDMA) treatment from postnatal days (P)11 to P20 leads to learning and memory deficits when the animals are tested as adults. Recently, the club drug 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) has gained popularity.

Objective: Due to the similarities between MDMA and 5-MeO-DIPT and the substitution of 5-MeO-DIPT for MDMA, the purpose of this study was to compare the developmental effects of these drugs.

Methods: Within a litter, animals were treated from P11 to P20 with either MDMA, 5-MeO-DIPT, or saline.

Results: MDMA-treated animals showed increased anxiety in a measure of defensive marble burying, as well as deficits in spatial and path integration learning. 5-MeO-DIPT-treated animals showed spatial learning deficits; however, there were no deficits observed in spatial memory or path integration learning. 5-MeO-DIPT-treated animals also showed hyperactivity in response to a challenge dose of methamphetamine.

Conclusions: The results show that treatment with either 5-MeO-DIPT or MDMA during development results in cognitive deficits and other behavioral changes but the pattern of effects is distinct for each drug.

Fig. 1

MDMA and 5-MeO-DIPT administration leads to reductions in body weight during dosing. Body weight (LS mean ± LS SEM) of offspring exposed to MDMA, 5-MeO-DIPT, or SAL from P11 to P20. Data represent the first and last dose of each day. During dosing, body weights were reduced in MDMA- and 5-MeO-DIPT-treated animals soon after treatment began compared to SAL-treated animals. Data are averaged across sex. *p<0.05 vs. SAL, #p<0.05 vs. MDMA

Fig. 2

Increased anxiety in MDMA-treated animals in a marble burying task. P11–20 MDMA-treated animals buried more marbles (LS mean ± LS SEM) and initiated burying sooner than SAL- and 5-MeO-DIPT-treated animals. 5-MeO-DIPT-treated animals initiated burying later than SAL- and MDMA-treated animals. Data are averaged across sex. *p<0.05 vs. SAL, #p<0.05 vs. 5-MeO-DIPT

Fig. 3

MDMA and 5-MeO-DIPT treatment induces spatial learning deficits in the MWM. Top: MDMA- and 5-MeO-DIPT-treated animals show deficits in path length (LS mean ± LS SEM) to the goal in phases 1 and 2 of the Morris water maze. In addition, MDMA-treated animals showed increased path lengths during phase 3 of the MWM. Bottom: MDMA-treated animals had greater average distances from the platform site than SAL- or 5-MeO-DIPT-treated animals. Data are averaged across sex. *p<0.05 vs. SAL; †p<0.10 vs. SAL; #p<0.05 vs. 5-MeO-D IPT; ‡p<0.10 vs. 5-MeO-DIPT

Fig. 4

MDMA treatment induces deficits in the Cincinnati water maze. MDMA treatment from P11 to P20 led to an increase in latency to reach the goal, errors, and start returns (LS mean ± LS SEM). 5-MeO-DIPT treatment did not alter CWM behavior. Data are averaged across sex. *p<0.05 vs. SAL; #p<0.05 vs. 5-MeO-DIPT

Fig. 5

5-MeO-DIPT treatment increases hyperactivity induced by methamphetamine challenge. 5-MeO-DIPT-treated animals had exaggerated increases in horizontal activity following methamphetamine administration compared to the increases seen in SAL- and MDMA-treated animals. Prior to testing, MDMA-treated animals were hypoactive compared to SAL-treated animals. No differences were observed between SAL-and MDMA-treated animals following methamphetamine treatment. Inset: Main effects of treatment. Data are averaged across sex. *p<0.05 vs. SAL; #p<0.05 vs. MDMA