Prior exposure to methylenedioxyamphetamine (MDA) induces serotonergic loss and changes in spontaneous exploratory and amphetamine-induced behaviors in rats

Harkin, Andrew; Connor, Thomas J.; Mulrooney, Jane B.; Kelly, John; Leonard, Brian E.

doi:10.1016/s0024-3205(00)01039-0

Cited by 35 publications

(25 citation statements)

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“…The present study found a clear loss of SERT binding sites in rats given the high-dose MDMA regime, in agreement with numerous previous studies showing 5-HT transporter loss in cortical, striatal, or hippocampal homogenates of rats given MDMA (Battaglia et al, 1987;Boot et al, 2002;Colado et al, 2001Colado et al, , 1995Harkin et al, 2001;O'Shea et al, 1998;Scanzello et al, 1993). A smaller number of studies have depicted the regional loss of SERT binding following MDMA in brain slices using quantitative autoradiographic Table 7 for quantitative analysis of binding data.…”

Section: Sert Bindingsupporting

confidence: 93%

“…At 12 weeks following MDMA or vehicle treatment, 18 of the 36 rats used in the study (n ¼ 6 per group) were decapitated using a guillotine, and their brains rapidly removed for neurochemical analysis. Five regions of interest were manually dissected out and frozen over dry ice using a method derived from that of Harkin et al (2001). Samples from the olfactory bulb, prefrontal cortex, striatum, hippocampus, and amygdala were individually placed in centrifuge tubes and stored in a freezer at À801C until assayed.…”

Section: Methodsmentioning

confidence: 99%

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Increased Anxiety 3 Months after Brief Exposure to MDMA (‘Ecstasy’) in Rats: Association with Altered 5-HT Transporter and Receptor Density

McGregor

Clemens

Plasse

et al. 2003

Neuropsychopharmacol

106

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Male Wistar rats were treated with 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') using either a high dose (4 Â 5 mg/kg over 4 h) or low dose (1 Â 5 mg/kg over 4 h) regimen on each of 2 consecutive days. After 10 weeks, rats were tested in the social interaction and emergence tests of anxiety. Rats previously given either of the MDMA dose regimens were significantly more anxious on both tests. After behavioral testing, and 3 months after the MDMA treatment, the rats were killed and their brains examined. Rats given the high-, but not the low-, dose MDMA treatment regimen exhibited significant loss of 5-hydroxytryptamine (5-HT) and 5-HIAA in the amygdala, hippocampus, striatum, and cortex. Quantitative autoradiography showed loss of SERT binding in cortical, hippocampal, thalamic, and hypothalamic sites with the high-dose MDMA regime, while low-dose MDMA only produced significant loss in the medial hypothalamus. Neither high-nor low-dose MDMA affected 5HT 1A receptor density. High-dose MDMA increased 5HT 1B receptor density in the nucleus accumbens and lateral septum but decreased binding in the globus pallidus, insular cortex and medial thalamus. Low-dose MDMA decreased 5HT 1B receptor density in the hippocampus, globus pallidus, and medial thalamus. High-dose MDMA caused dramatic decreases in cortical, striatal, thalamic, and hypothalamic 5HT 2A / 2C receptor density, while low-dose MDMA tended to produce similar effects but only significantly in the piriform cortex. These data suggest that even brief, relatively low-dose MDMA exposure can produce significant, long-term changes in 5-HT receptor and transporter function and associated emotional behavior. Interestingly, long-term 5-HT depletion may not be necessary to produce lasting effects on anxiety-like behavior after low-dose MDMA.

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Section: Sert Bindingsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Increased Anxiety 3 Months after Brief Exposure to MDMA (‘Ecstasy’) in Rats: Association with Altered 5-HT Transporter and Receptor Density

McGregor

Clemens

Plasse

et al. 2003

Neuropsychopharmacol

106

View full text Add to dashboard Cite

show abstract

“…In this experiment it was observed that MDMA attenuated inhibitory responses to 5-HT that otherwise occurred. And, numerous, more recent animal investigations have reported that repeated exposure to MDMA at higher doses diminishes 5-HT-mediated changes in a variety of phenomenological behaviors such as exploratory-oriented locomotion (Harkin et al, 2001) and social interaction (Clemens et al, 2004). Consistent with these behavioral effects are findings from studies showing MDMA-based depletion of 5-HT stores across several brain regions (cf.…”

Section: Discussionmentioning

confidence: 79%

The effects of concurrent administration of (±)3,4-Methylenedioxymethamphetamine and cocaine on conditioned place preference in the adult male rat

Diller

Rocha

Cardon

et al. 2007

Pharmacology Biochemistry and Behavior

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Conditioned place preference (CPP), a commonly used model for studying the role of contextual cues in drug reward and drug seeking, was employed to explore possible behavioral interactions between (±)3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") and cocaine. On each of four occasions, adult male rats received one of three doses of MDMA (0 mg/kg, 5 mg/kg, 10 mg/kg; administered subcutaneously [s.c.]) combined with one of three doses of cocaine (0 mg/kg, 2.5 mg/ kg, 5 mg/kg; administered intraperitoneally [i.p.]), and were then tested in a CPP paradigm. The results showed MDMA-induced CPP at a unit dose of 5 mg/kg, but at the 10 mg/kg dose there was a return to baseline (control) performance levels. For cocaine alone, CPP increased in a linear fashion as the drug dose was increased. Concurrent administration resulted in antagonism of each drug, but there was evidence that this pattern was reversible at higher doses of the respective drugs. These data are instructive insofar as they suggest that the behavioral and neurochemical effects of MDMA and cocaine presented in isolation are dramatically altered when the two drugs are presented in combination.

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“…Somewhat similar results have been reported by Fone et al (2002) following administration of MDMA to adolescent rats and subsequent testing of open field behavior and social interaction up to 29 days later; although in this study the increased anxiety response was not accompanied by PHARMACOLOGY OF MDMA any measurable neurotoxic loss of 5-HT. Prior administration of MDA has also been reported to produce a decrease in open field behavior (Harkin et al, 2001). In contrast, Mechan et al (2002b) reported both an increase in open field behavior and an apparent anxiolytic response on the elevated plus maze when rats were tested 73 to 80 days after a neurotoxic dose of MDMA.…”

Section: Long-term Functionalmentioning

confidence: 99%

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

et al. 2003

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Prior exposure to methylenedioxyamphetamine (MDA) induces serotonergic loss and changes in spontaneous exploratory and amphetamine-induced behaviors in rats

Cited by 35 publications

References 0 publications

Increased Anxiety 3 Months after Brief Exposure to MDMA (‘Ecstasy’) in Rats: Association with Altered 5-HT Transporter and Receptor Density

Increased Anxiety 3 Months after Brief Exposure to MDMA (‘Ecstasy’) in Rats: Association with Altered 5-HT Transporter and Receptor Density

The effects of concurrent administration of (±)3,4-Methylenedioxymethamphetamine and cocaine on conditioned place preference in the adult male rat

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

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