Effects of MDMA on olfactory memory and reversal learning in rats

Hawkey, Andrew; April, L. Brooke; Galizio, Mark

doi:10.1016/j.nlm.2014.06.012

Cited by 11 publications

(15 citation statements)

References 38 publications

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“…These results closely parallel the present findings with multiple stimuli to remember in the OST—generally impairment that was task-independent and often occurred at relatively low doses was found. These findings were also quite similar to a previous study from our laboratory which found that MDMA also produced only nonselective impairment of responding with the OST/SDC procedure (Hawkey, April, & Galizio, 2014). Although none of the rats showed increased accuracy after either methamphetamine or methylphenidate, it must be noted that baseline levels were high in both tasks and it is possible that a ceiling effect may have obscured observation of enhancement.…”

Section: Discussionsupporting

confidence: 91%

Behavioral pharmacology of the odor span task: Effects of flunitrazepam, ketamine, methamphetamine and methylphenidate

Galizio¹,

April²,

Deal³

et al. 2016

J Exper Analysis Behavior

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The Odor Span Task is an incrementing non-matching-to-sample procedure that permits the study of behavior under the control of multiple stimuli. Rats are exposed to a series of odor stimuli and selection of new stimuli is reinforced. Successful performance thus requires remembering which stimuli have previously been presented during a given session. This procedure has been frequently used in neurobiological studies as a rodent model of working memory; however, only a few studies have examined the effects of drugs on performance in this task. The present experiments explored the behavioral pharmacology of a modified version of the Odor Span Task by determining the effects of stimulant drugs methylphenidate and methamphetamine, NMDA antagonist ketamine, and positive GABAA modulator flunitrazepam. All four drugs produced dose-dependent impairment of performances on the Odor Span Task, but for methylphenidate and methamphetamine, these occurred only at doses that had similar effects on performance of a simple odor discrimination. Generally, these disruptions were based on omission of responding at the effective doses. The effects of ketamine and flunitrazepam were more selective in some rats. That is, some rats tested under flunitrazepam and ketamine showed decreases in accuracy on the Odor Span Task at doses that did not affect simple discrimination performance. These selective effects indicate disruption of within-session stimulus control. Overall, these findings support the potential of the Odor Span Task as a baseline for the behavioral pharmacological analysis of remembering.

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Section: Discussionsupporting

confidence: 91%

Behavioral pharmacology of the odor span task: Effects of flunitrazepam, ketamine, methamphetamine and methylphenidate

Galizio¹,

April²,

Deal³

et al. 2016

J Exper Analysis Behavior

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show abstract

“…Doses of 0. 1, 0.3, 0.32, 0.75, 1.0, 1.25, 1.7, 1.75, 1.8, 2.0, and 2.25 mg/kg produced no effects on working memory when animals were tested on-drug on the DMS (LeSage et al, 1993;Frederick et al, 1995a,b;Harper et al, 2005), OST (Hawkey et al, 2014), DA (Young et al, 2005), RAM (Braida et al, 2002;Kay et al, 2010), or MWM (Galizio et al, 2014) tasks. Doses of 0.3, 0.75, 1.0, 1.25, 1.7, and 2.25 mg/kg produced no effects on spatial learning and memory when animals were tested on-drug on the MWM (Galizio et al, 2014), RAM (Kay et al, 2010), or SD (Young et al, 2005) tasks.…”

Section: B Findings By Dosementioning

confidence: 99%

Cognitive Effects of MDMA in Laboratory Animals: A Systematic Review Focusing on Dose

Pantoni

Anagnostaras

2019

Pharmacol Rev

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Methylenedioxymethamphetamine (MDMA) is a synthetic, psychoactive drug that is primarily used recreationally but also may have some therapeutic value. At low doses, MDMA produces feelings of relaxation, empathy, emotional closeness, and euphoria. Higher doses can produce unpleasant psychostimulantand hallucinogen-like adverse effects and therefore are usually not taken intentionally. There is considerable evidence that MDMA produces neurotoxicity and cognitive deficits at high doses; however, these findings may not generalize to typical recreational or therapeutic use of low-dose MDMA. Here, we systematically review 25 years of research on the cognitive effects of MDMA in animals, with a critical focus on dose. We found no evidence that doses of less than 3 mg/kg MDMA-the dose range that users typically take-produce cognitive deficits in animals. Doses of 3 mg/kg or greater, which were administered most often and frequently ranged from 5 to 20 times greater than an average dose, also did not produce cognitive deficits in a slight majority of experiments. Overall, the preclinical evidence of MDMA-induced cognitive deficits is weak and, if anything, may be the result of unrealistically high dosing. While factors associated with recreational use such as polydrug use, adulterants, hyperthermia, and hyponatremia can increase the potential for neurotoxicity, the short-term, infrequent, therapeutic use of ultra low-dose MDMA is unlikely to pose significant cognitive risks. Future studies must examine any adverse cognitive effects of MDMA using clinically relevant doses to reliably assess its potential as a psychotherapeutic.

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“…For example, both scopolamine and MDMA produced dose-dependent decreases in OST accuracy and span length, but significant impairment was only noted at doses that also impaired simple discrimination accuracy (Galizio et al, 2013; Hawkey et al, 2014). Thus, neither drug appeared to act in any selective fashion on within session remembering or to affect the number of stimuli rats could remember.…”

Section: Control By Multiple Stimuli: the Odor Span Taskmentioning

confidence: 99%

Olfactory stimulus control and the behavioral pharmacology of remembering.

Galizio

2016

Behavior Analysis: Research and Practice

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Behavior analytic approaches and techniques have much to offer to the study of remembering. There is currently great interest in the development of animal models of human memory processes in order to enhance understanding of the neurobiology of memory and treatment of dementia and related disorders. Because rodent models are so important in contemporary neuroscience and genetics, development of procedures to study various forms of memory in rodents is a point of emphasis. The sense of smell plays an important role in rodent behavior and use of olfactory stimuli has permitted demonstrations of complex forms of stimulus control that have also served as baselines for studying drug effects on remembering. This article focuses on the effects of drugs on behavior maintained by two related procedures: delayed matching-to-sample with odors and the Odor Span Task. These types of procedures provide an opportunity to explore drug effects on behavior maintained by multiple stimuli and across a range of delay intervals with potential to advance analysis of the behavioral pharmacology of remembering.

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Effects of MDMA on olfactory memory and reversal learning in rats

Cited by 11 publications

References 38 publications

Behavioral pharmacology of the odor span task: Effects of flunitrazepam, ketamine, methamphetamine and methylphenidate

Behavioral pharmacology of the odor span task: Effects of flunitrazepam, ketamine, methamphetamine and methylphenidate

Cognitive Effects of MDMA in Laboratory Animals: A Systematic Review Focusing on Dose

Olfactory stimulus control and the behavioral pharmacology of remembering.

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