Behavioral effects of (�) 3,4-methylenedioxyamphetamine (MDA) and (�) 3,4-methylenedioxymethamphetamine (MDMA) in the pigeon: interactions with noradrenergic and serotonergic systems

Abstract

The effects of three amphetamine analogs were assessed in pigeons key pecking under a multiple 3-min fixed-interval (FI), 30 response fixed-ratio (FR) schedule of food presentation. At doses between 0.1 and 10.0 mg/kg, (+-) 3,4-methylenedioxyamphetamine (MDA), (+-) 3,4-methylenedioxymethamphetamine (MDMA), and (+-)-N-ethyl-3,4-methylenedioxyamphetamine (MDE) either had no effect or decreased response rates in both components of the multiple schedule in a dose-dependent manner. MDA was at least 1 log unit more potent than the other two compounds. Metergoline (0.1-1.0 mg/kg), a serotonin (5-HT) antagonist with comparable affinity for the 5-HT1 and 5-HT2 receptor subtypes, blocked the rate-decreasing effects of 3.0 mg/kg MDA in both components of the multiple schedule, but did not affect the MDMA dose-response curve. The 5-HT2 receptor antagonist ketanserin (0.1-3.0 mg/kg) also restored FI and FR responding that was decreased by 3.0 mg/kg MDA, but had no effect on responding suppressed by MDMA. The noradrenergic alpha-1 antagonist prazosin (0.3-3.0 mg/kg) blocked the behavioral effects of 3.0 mg/kg MDMA at doses that did not attenuate MDA's rate-decreasing effects. These results indicate that although MDA and MDMA are structurally similar and have similar behavioral effects, their actions appear to be mediated through different neurotransmitter systems.

MDMA and memory: the acute and chronic effects of MDMA in pigeons performing under a delayed-matching-to-sample procedure

“…The rate-reducing effects shown here are consistent with results reported with mice responding under a FR 20 schedule Rosecrans and Glennon 1987) and in pigeons responding under a multiple FR 30 FI 3-min schedule (Nader et al 1989). They also agree with results reported by Thompson et al (1987), who demonstrated that acute administrations of MDMA decreased rates of responding in monkeys performing under a repeated acquisition procedure.…”

“…Throughout the experiment, drug and vehicle control injections were administered 10 min prior to experimental sessions. Doses and presession injection times were selected on the basis of previous reports (Evans and Johanson 1986;Nader et al 1989) and pilot data from our laboratory. Each bird received at least two, but no more than three, administrations of every dose.…”

“…In mice, acute administrations of MDMA decreased response rates maintained under a fixed-ratio 20 (FR 20) schedule of food delivery in generally dose-dependent fashion Rosecrans and Glennon 1987). In pigeons, the drug when given acutely produced dose-dependent decreases in response rates under both components of a multiple FR 30 fixed-interval 3-min (FI 3-min) schedule of food delivery (Nader et al 1989). Acute administrations of MDMA also decreased rates of responding in monkeys performing under a repeated acquisition procedure, although the drug did not affect learning or performance accuracy (Thompson et al 1987).…”

MDMA (N-methyl-3,4-methylenedioxyamphetamine) and its stereoisomers: Similarities and differences in behavioral effects in an automated activity apparatus in mice

“…In humans, MDMA reportedly produces psychological and physiological effects that include a sense of euphoria, greater tolerance of the views and feelings of other people, and increases in wakefulness, endurance, well being, sexual arousal, and social abilities (e.g., Cohen, 1995;Peroutka et al 1988;Siegel, 1986). Although the exact mechanism(s) of action of MDMA is not known with certainty, its effects are thought to be the result of biochemical interactions that influence, to various degrees, the brain monoamine neurotransmitters serotonin (5-HT), dopamine (DA), and norepinephrine (NE) (e.g., Baumann et al 2007;Liechti et al 2000;Liechti and Vollenweider, 2001;Nader et al 1989;Stuerenberg et al 2002).…”

Effects of repeated MDMA administration on the motivation for palatable food and extinction of operant responding in mice

“…In agreement with our results, previous studies have reported detrimental effects of acute MDMA on instrumental responding in different laboratory animals. Thus, rate-decreasing effects of MDMA on FR schedules of food reinforcement have been observed in pigeons (Nader et al 1989), rats (Li et al 1989;Nagilla et al 1998) and mice (Glennon et al 1987;Miczek and Haney 1994). Performance under PR schedules is also disrupted by acute doses of MDMA (1.0 mg/kg) in monkeys (Frederick and Paule 1997) and in rats (3.2 and 5.6 mg/kg; Laraway et al 2003).…”