Rats preexposed to MDMA display attenuated responses to its aversive effects in the absence of persistent monoamine depletions

Abstract

Prior MDMA experience weakened the ability of MDMA to induce taste aversions. This attenuation of MDMA's aversive effects may occur with low doses that do not persistently alter monoamine levels.

Synergistic effects of MDMA and ethanol on behavior: Possible effects of ethanol on dopamine D2‐receptor‐related signaling

“…The precise mechanisms by which ethanol regulates MDMA‐induced behavioral changes are not yet clear. However, a large and growing body of evidence has demonstrated that activation of either D 1 ‐, D 2 ‐, or 5‐HT 2 ‐receptor contributes to the expression of behavioral changes, such as increases in locomotor activity, stereotyped behaviors, and reinforcing/rewarding and discriminative stimulus effects induced by psychostimulants including MDMA in animals 29–33 . Locomotor activity produced by psychostimulants could be suppressed by several compounds through non‐specific mechanisms, such as sedative effects.…”

Age differences in (±) 3,4‐methylenedioxymethamphetamine (MDMA)‐induced conditioned taste aversions and monoaminergic levels

“…In particular, MDMA induced dose-dependent taste aversions in both adolescent and adult animals (see also Albaugh et al, 2011; Lin et al, 1993; Lin et al, 1994), but aversions were significantly weaker in the adolescent subjects. Blunted taste aversions were evident in the doses at which the aversions were acquired, the rate at which the aversions were first evident and the degree of suppression (in both the one- and two-bottle assessments) displayed by the animals.…”

“…Thus, speculating that there might be differences in this aversive effect in various age groups must be made cautiously. This is especially the case for compounds such as MDMA for which the characterization of its ability to induce aversions is relatively limited (see Albaugh et al, 2011; Lin et al, 1993; Lin et al, 1994). …”

“…Drugs MDMA (generously supplied by the National Institute on Drug Abuse) was dissolved in sterile isotonic saline (Sigma-Aldrich, St. Louis, MO) at a concentration of 2 mg/ml and was filtered through a .2 mm syringe filter to remove any possible contaminants before being administered subcutaneously at a dose of 1.0, 1.8, or 3.2 mg/kg (see Albaugh et al, 2011;Lin et al, 1993). Sterile isotonic saline was also filtered prior to being administered to vehicle control animals at a volume equal to the highest dose of MDMA administered (3.2 mg/kg).…”

“…MDMA is self-administered in rodents (de la Garza, Fabrizio, & Gupta, 2007; Schenk, Gittings, Johnstone, & Daniela, 2003), dose-dependently lowers intracranial self-stimulation thresholds (Lin, Jackson, Atrens, Christie, & McGregor, 1997; Reid, Hubbell, Tsai, Fishkin, & Amendola, 1996) and produces dose-dependent CPP in both adult (Braida, Iosuè, Pegorini, & Sala, 2005; Marona-Lewicka, Rhee, Sprague, & Nichols, 1996) and adolescent (Catlow, Badanich, Sponaugle, Rowe, Song, Rafalovich, Sava, Kirstein, & Sanchez-Ramos, 2010) rats, all measures indicative of MDMA’s rewarding properties. Conversely, MDMA produces taste aversions to solutions associated with its administration in adult Wistar (Lin, Atrens, Christie, Jackson, & McGregor, 1993; Lin, McGregor, Atrens, Christie, & Jackson, 1994) and Sprague-Dawley (Albaugh, Rinker, Baumann, Sink, & Riley, 2011) rats, although no assessments have examined MDMA-induced taste aversions in adolescent rats of either strain. Accordingly, in the present series of studies MDMA-induced taste aversions were assessed in both adolescent (Experiment 1) and adult (Experiment 2) male Sprague-Dawley rats.…”