Partial lesion of the serotonergic system by a single dose of MDMA results in behavioural disinhibition and enhances acute MDMA-induced social behaviour on the social interaction test

Andó, Rómeó D.; Benko, Anita; Ferrington, Linda; Kirilly, Eszter; Kelly, Paul A.; Bagdy, György

doi:10.1016/j.neuropharm.2005.12.010

Cited by 44 publications

(35 citation statements)

References 58 publications

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“…However, the same studies showed that aggressive mood was elevated during the mid-week period following a weekend of Ecstasy use, a phenomenon that could be related to MDMA-induced depletion of 5-HT (Krakowski, 2003;Miczek et al, 2002). In accordance with the human literature, rats given relatively low doses of MDMA showed increased social interaction and decreased aggressive behavior while the drug is still 'on board' (Morley and McGregor, 2000), whereas 5-HT-depleting doses of MDMA produced later increases in aggressiveness in the social interaction test (Ando et al, 2006), though not in the resident-intruder paradigm (Kirilly et al, 2005). When the social interaction test was carried out in the present study, many of the control (SAL/SAL) rats fought when confronted with an unfamiliar male, whereas the animals in the SAL/MDMA group unexpectedly showed significantly less of this behavior.…”

Section: Discussionsupporting

confidence: 59%

Dissociation of the Neurochemical and Behavioral Toxicology of MDMA (‘Ecstasy’) by Citalopram

Piper

Fraiman

Owens

et al. 2007

Neuropsychopharmacol

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High or repeated doses of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy') produce long-lasting deficits in several markers of serotonin (5-HT) system integrity and also alter behavioral function. However, it is not yet clear whether MDMA-induced serotonergic neurotoxicity is responsible for these behavioral changes or whether other mechanisms are involved. The present experiment tested the hypothesis that blocking serotonergic neurotoxicity by pretreatment with the selective 5-HT reuptake inhibitor citalopram will also prevent the behavioral and physiological consequences of an MDMA binge administration. Male, SpragueDawley rats (N ¼ 67) received MDMA (4 Â 10 mg/kg) with or without citalopram (10 mg/kg) pretreatment. Core temperature, ejaculatory response, and body weight were monitored during and immediately following drug treatments. A battery of tests assessing motor, cognitive, exploratory, anxiety, and social behaviors was completed during a 10-week period following MDMA administration. Brain tissue was collected at 1 and 10 weeks after drug treatments for measurement of regional 5-HT transporter binding and (for the 1-week samples) 5-HT and 5-HIAA concentrations. Citalopram pretreatment blocked MDMA-related reductions in aggressive and exploratory behavior measured in the social interaction and hole-board tests respectively. Such pretreatment also had the expected protective effect against MDMA-induced 5-HT neurotoxicity at 1 week following the binge. In contrast, citalopram did not prevent most of the acute effects of MDMA (eg hyperthermia and weight loss), nor did it block the decreased motor activity seen in the binge-treated animals 1 day after dosing. These results suggest that some of the behavioral and physiological consequences of a high-dose MDMA regimen in rats are mediated by mechanisms other than the drug's effects on the serotonergic system. Elucidation of these mechanisms requires further study of the influence of MDMA on other neurotransmitter systems.

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Section: Discussionsupporting

confidence: 59%

Dissociation of the Neurochemical and Behavioral Toxicology of MDMA (‘Ecstasy’) by Citalopram

Piper

Fraiman

Owens

et al. 2007

Neuropsychopharmacol

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“…On the other hand, in behavioral studies in rats, increase or decline in locomotor activity has frequently been interpreted as psychomotor agitation and retardation, respectively [25,26]. Based on this, decline in both rearing behavior and locomotor activity (CAE in the EPM test) as well as the lack of a significant anxiogenic-like effect in our study suggest that blockade of CB 1 receptors produces psychomotor retardation rather than a pronounced anxiety-like effect.…”

Section: Discussionsupporting

confidence: 55%

Blockade of Serotonin 2C Receptors with SB-242084 Moderates Reduced Locomotor Activity and Rearing by Cannabinoid 1 Receptor Antagonist AM-251

et al. 2019

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The endocannabinoid and serotonin (5-HT) systems have key roles in the regulation of several physiological functions such as motor activity and food intake but also in the development of psychiatric disorders. Here we tested the hypothesis, whether blockade of serotonin 2C (5-HT_2C) receptors prevents the reduced locomotor activity and other behavioral effects caused by a cannabinoid 1 (CB₁) receptor antagonist. As a pretreatment, we administered SB-242084 (1 mg/kg, ip.), a 5-HT_2C receptor antagonist or vehicle (VEH) followed by the treatment with AM-251 (5 or 10 mg/kg, ip.), a CB₁ receptor antagonist or VEH. The effects of the two drugs alone or in co-administration were investigated in social interaction (SI) and elevated plus maze (EPM) tests in male Wistar rats. Our results show that AM-251 decreased the time spent with rearing in the SI test and decreased locomotor activity in EPM test. In contrast, SB-242084 produced increased locomotor activity in SI test and evoked anxiolytic-like effect in both SI and EPM tests. When applied the drugs in combination, these behavioral effects of AM-251 were moderated by SB-242084. Based on these findings, we conclude that certain unwanted behavioral effects of CB₁ receptor antagonists could be prevented by pretreatment with 5-HT_2C receptor antagonists.

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“…4A) and higher frequency of rearing behavior (Fig. 3B), which is a non-social exploratory behavior in this test context (Ando et al, 2006;O'Tuathaigh et al, 2010O'Tuathaigh et al, , 2008. EE was not able to prevent these behaviors that mimic negative symptoms.…”

Section: Discussionmentioning

confidence: 80%

Peripubertal exposure to environmental enrichment prevents schizophrenia-like behaviors in the SHR strain animal model

Santos

Peres

Diana

et al. 2016

Schizophrenia Research

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Partial lesion of the serotonergic system by a single dose of MDMA results in behavioural disinhibition and enhances acute MDMA-induced social behaviour on the social interaction test

Cited by 44 publications

References 58 publications

Dissociation of the Neurochemical and Behavioral Toxicology of MDMA (‘Ecstasy’) by Citalopram

Dissociation of the Neurochemical and Behavioral Toxicology of MDMA (‘Ecstasy’) by Citalopram

Blockade of Serotonin 2C Receptors with SB-242084 Moderates Reduced Locomotor Activity and Rearing by Cannabinoid 1 Receptor Antagonist AM-251

Peripubertal exposure to environmental enrichment prevents schizophrenia-like behaviors in the SHR strain animal model

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