Treatment with MDMA from P11–20 disrupts spatial learning and path integration learning in adolescent rats but only spatial learning in older rats

Skelton, Matthew R.; Williams, Michael T.

doi:10.1007/s00213-006-0563-4

Cited by 41 publications

(63 citation statements)

References 34 publications

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“…Among other things, adolescence in humans is associated with high levels of sensation-seeking behavior and a desire for novelty (Adriani & Laviola, 2004). However, in addition to the reported learning, memory, impulsivity, and cognitive impairments described here and elsewhere (e.g., Compton et al, 2011;Green et al, 2003;Skelton et al, 2006Skelton et al, , 2009) the use of these drugs appears to carry a number of inherent risks. For example, among the reported long-term consequences associated with the use of MDMA are nonmemorial (e.g., Parkinson's Disease; Morton, 2005) deficits.…”

Section: Discussionmentioning

confidence: 68%

Differentiation of MDMA or 5-MeO-DIPT induced cognitive deficits in rat following adolescent exposure.

Compton¹,

Selinger²,

Westman³

et al. 2011

Psychology & Neuroscience

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The so-called "club drug" Foxy or Methoxy Foxy (5-Methoxy-N,N-di(iso)propyltryptamine hydrochloride; 5-MeO-DIPT) is a newer drug of abuse that has recently gained in popularity among recreational users as an alternative to MDMA (Ecstasy). While considerable research into the consequences of MDMA use is available, much remains unknown about the neurobiological consequences of 5-MeO-DIPT use. In the present study, beginning at 35 days of age adolescent rats were given repeated injections of 10 mg/kg of 5-MeO-DIPT, MDMA, or a corresponding volume of isotonic saline. Adult animals (135 days old) were trained and tested on a number of tasks designed to assess the impact, if any, and severity of 5-MeO-DIPT and MDMA, on a series of spatial and nonspatial memory tasks. Both the 5-MeO-DIPT-and the MDMA-treated rats were able to master the spatial navigation tests where the task included a single goal location and all groups performed comparably on these phases of training and testing. Conversely, the performance of both groups of the drug-treated rats was markedly inferior to that of the control animals on a task where the goal was moved to a new location and on a response learning task, suggesting a lack of flexibility in adapting their responses to changing task demands. In addition, in a response learning version of a learning set task, 5-MeO-DIPT rats made significantly more working memory errors than MDMA or control rats. Results are discussed in terms of observed alterations in serotonin activity in the forebrain and the consequences of compromised serotoninergic systems on cognitive processes.

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Section: Discussionmentioning

confidence: 68%

Differentiation of MDMA or 5-MeO-DIPT induced cognitive deficits in rat following adolescent exposure.

Compton¹,

Selinger²,

Westman³

et al. 2011

Psychology & Neuroscience

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“…During probe trials, MDMA treatment groups showed decreased time in the target quadrant for animals beginning testing on P30, but not in animals that began testing at P40, whereas P180 and P360 tested animals showed deficits depending on the phase of the MWM procedure. MDMA-treated animals tested on P180 showed decreased time in the target quadrant during the acquisition and reversal phases of probe trial testing compared with saline-treated animals, whereas at P360 MDMAtreated animals showed deficits during the acquisition and reduced platform probe trials (Skelton et al, 2006). It seems that the function of the 5-HT receptors during memory consolidation changes as animals age: downregulation is seen in younger animals, whereas upregulation is observed in aged animals (Meneses and Perez-Garcia, 2007).…”

Section: Behaviormentioning

confidence: 92%

“…It has been shown that MDMA administration to neonatal rats decreases the rate of weight gain (Broening et al, 1995(Broening et al, , 2001Koprich et al, 2003a;Williams et al, 2003;Meyer et al, 2004;Vorhees et al, 2004;Skelton et al, 2006). This anorectic effect of MDMA continues several weeks after administration of the drug is discontinued; however, weights are similar by adulthood (Broening et al, 2001;Williams et al, 2003;Vorhees et al, 2004;Skelton et al, 2006). In adults it has been shown that MDMA causes a hyperthermic effect when ambient temperatures are over approximately 21°C.…”

Section: Effects Of Neonatal Exposure To Mdma In Animals General Charmentioning

confidence: 99%

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Developmental effects of 3,4-methylenedioxymethamphetamine: a review

Skelton

Williams

Vorhees

2008

Behavioural Pharmacology

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Abstract± 3,4-Methylenedioxymethamphetamine (MDMA) is a chemical derivative of amphetamine that has become a popular drug of abuse and has been shown to deplete serotonin in the brains of users and animals exposed to it. To date, most studies have investigated the effects of MDMA on adult animals. With a majority of users of MDMA being young adults, the chances of the users becoming pregnant and exposing the fetuses to MDMA are also a concern. Evidence to date has shown that developmental exposure to MDMA results in learning and memory impairments in the Morris water maze, a task known to be sensitive to hippocampal disruption, when the animals are tested as adults. Developmental MDMA exposure leads to hypoactivity in the offspring as adults but does not affect outcome on tests of anxiety. MDMA administration decreases pup weight, increases corticosterone and brain-derived neurotrophic factor levels during treatment while decreasing brain levels of serotonin; a decrease that initially dissipates and then reappears in adulthood. Neonatal MDMA exposure increases the sensitivity of the serotonin 1A receptor, a possible mechanism underlying the learning and memory deficits seen. Taken together, the evidence shows that MDMA exposure has adverse effects on the developing brain and behavior. The animal and human data on developmental MDMA exposure are reviewed and their public health implications discussed.

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“…Numerous studies have associated heavy or chronic ecstasy use to persistent cognitive deficits in humans (Morgan 1999;Bhattachary and Powell 2001;Dafters 2006;Quednow et al 2006;Zakzanis and Campbell 2006;Kalechstein et al 2007). Experiments in animals have shown learning and memory alterations in rats (Sprague et al 2003;Able et al 2006;Skelton et al 2006), monkeys (Taffe et al 2001;Frederick and Paule 1997), and mice Rosecrans and Glennon 1987) using a variety of behavioural paradigms. However, pinpointing the underlying mechanism related to these deficits has been difficult, primarily due to the varying profiles of MDMA effects in different species (see Easton and Marsden 2006 for review).…”

Section: Introductionmentioning

confidence: 99%