Effects of MDMA on Complex Brain Function in Laboratory Animals
Section snippets
INTRODUCTION
3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA or “Ecstasy”) is a phenylisopropylamine amphetamine analog possessing both stimulant-like (dopaminergic) and hallucinogen-like (serotonergic) properties 42, 50, 68, presumably as a result of its serotonin (5-HT) and dopamine (DA) releasing effects, and/or its ability to inhibit 5-HT and/or DA reuptake or monoamine oxidase 7, 25, 33, 42. In laboratory animals, the acute behavioral effects of MDMA appear to be qualitatively more like stimulants than
ACUTE EFFECTS OF MDMA ON COMPLEX BRAIN FUNCTION
In our laboratory at the National Center for Toxicological Research (NCTR), the acute effects of MDMA were assessed in three adult male rhesus monkeys using performance in the NCTR Operant Test Battery (OTB) [15]. The specific tasks contained in the OTB have been described in detail elsewhere [61], and a diagram of the OTB behavioral panel is presented in Fig. 1. The OTB currently consists of five tasks thought to engender or elicit behaviors that are believed to model aspects of time
CHRONIC EFFECTS OF MDMA ON COMPLEX BRAIN FUNCTIONS
As mentioned previously, short course, high dose MDMA administration has been shown to cause long-lasting changes in 5-HT systems (i.e. decreased brain 5-HT and 5-HIAA concentrations, and suspected 5-HT axon terminal degeneration) in laboratory animals. However, from the relatively few studies that have compared post-treatment behavior to pre-exposure behavior or to the behavior of non-treated controls, few significant differences have been reported. The majority of these experiments have not
SUMMARY
In MDMA-naïve animals, operant schedules in which correct performance is thought to depend upon the learning and time estimation capabilities of subjects appear to be more sensitive to the acute effects of MDMA than tasks thought to depend upon short-term memory and visual discriminations. Schedule-controlled operant behaviors thought to assess aspects of motivation to work for food also seem to be particularly sensitive to the acute effects of MDMA, possibly reflecting the anorectic properties
Acknowledgements
D. L. Frederick was supported through an appointment to the Oak Ridge Associated Universities Postgraduate Research Program. The authors thank Jeannette Coleman for her assistance in the preparation of this manuscript, and the animal care personnel at the NCTR (Crystal Brown, Larry Dawson, James Henderson, Teresa Howard, Pamela Morgan, Randy Thompson, Arnold Tripp, Josephine Watson, O. T. Watson and Betty White) for their excellent care and handling of the monkeys.
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Single and repeated exposures to the volatile anesthetic isoflurane do not impair operant performance in aged rats
2016, NeuroToxicologyCitation Excerpt :The PR task requires that the subject perform an increasing number of lever presses for each subsequent reinforcer and has widely been used as a classic method for evaluating motivation in rodents (Hodos and Kalman, 1963; Hutsell and Newland, 2013; Jones et al., 1995; Oleson et al., 2011; Reichelt et al., 2016). Research has demonstrated the PR and IRA tasks to be sensitive to various psychoactive compounds in rats (Ferguson and Paule, 1996; Mayorga et al., 2000; Popke et al., 2000a,b) and monkeys (Buffalo et al., 1994; Ferguson and Paule, 1993; Frederick and Paule, 1997; Paule, 1990), including the anesthetic, ketamine (Paule et al., 2011), and specific behavioral profiles can be created for such substances using these tasks (Paule, 1990). Further, the IRA and PR tasks are exemplary translational research tools.
The effects of binge MDMA on acquisition and reversal learning in a radial-arm maze task
2011, Neurobiology of Learning and MemoryCitation Excerpt :Ecstasy users have reported having to increase the amount of the drug they take to experience the positive effects of the drug (Parrott, 2001) indicating they become tolerant to the effects of the drug. However, animal studies have found mixed results where some studies have found evidence of drug tolerance occurring after repeated exposure to the drug (Brennan & Schenk, 2006; Frederick & Paule, 1997; Frederick et al., 1995, 1998; LeSage et al., 1993; Marston et al., 1999; Piper, Vu, Safain, Oliver, & Meyer, 2006; Shankaran & Gudelsky, 1999) and others have reported repeated MDMA exposure produces behavioral sensitization (Kalivas, Duffy, & White, 1998; Li, Marek, Vosmer, & Seiden, 1989; Modi, Yang, Swann, & Dafny, 2006; Moyano, Del Rio, & Frechilla, 2005; Spanos & Yamamoto, 1989). The reasons why such conflicting findings as to whether repeated MDMA exposure results in tolerance or sensitization are unclear.
Differential effects of MDMA and scopolamine on working versus reference memory in the radial arm maze task
2010, Neurobiology of Learning and MemoryTolerance to 3,4-methylenedioxymethamphetamine in rats exposed to single high-dose binges
2008, NeuroscienceCitation Excerpt :The blunted responsiveness to MDMA shown here agrees with previous reports of tolerance to diverse effects of MDMA in rats, including anorexia (Zacny et al., 1990), discriminative stimulus properties (Schechter, 1991; Virden and Baker, 1999), hyperthermia (Shankaran and Gudelsky, 1999; Piper et al., 2006) and locomotor activity (Callaway and Geyer, 1992; Brennan and Schenk, 2006). Tolerance to behavioral actions of MDMA is also well documented in non-human primates (Frederick et al., 1995; Frederick and Paule, 1997; Fantegrossi et al., 2004; Fantegrossi, 2007). On the other hand, a number of studies in rodents provide evidence for sensitized responsiveness after repeated MDMA exposure (Poland et al., 1997; Kalivas et al., 1998; Giorgi et al., 2005), suggesting tolerance development is not a universal outcome.
The prevalence of MDMA/MDA in both hair and urine in drug users
2005, Forensic Science InternationalEffects of 3,4-methylenedioxymethamphetamine and related amphetamines on autonomic and behavioral thermoregulation
2005, Pharmacology Biochemistry and Behavior