Home > Investigation of the mechanisms mediating MDMA "Ecstasy"-induced increases in cerebro-cortical perfusion determined by btASL MRI.

Rouine, J and Kelly, ME and Jennings-Murphy, C and Duffy, P and Gorman, I and Gormley, S and Kerskens, CM and Harkin, Andrew (2014) Investigation of the mechanisms mediating MDMA "Ecstasy"-induced increases in cerebro-cortical perfusion determined by btASL MRI. Psychopharmacology, 232, (9), pp. 1501-1513. doi: 10.1007/s00213-014-3790-0.

RATIONALE: Acute administration of the recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has previously been shown to increase cerebro-cortical perfusion as determined by bolus-tracking arterial spin labelling (btASL) MRI.

OBJECTIVES: The purpose of the current study was to assess the mechanisms mediating these changes following systemic administration of MDMA to rats.

METHODS: Pharmacological manipulation of serotonergic, dopaminergic and nitrergic transmission was carried out to determine the mechanism of action of MDMA-induced increases in cortical perfusion using btASL MRI.

RESULTS: Fenfluramine (10 mg/kg), like MDMA (20 mg/kg), increased cortical perfusion. Increased cortical perfusion was not obtained with the 5-HT2 receptor agonist 2,5-dimethoxy-4-iodophenyl-aminopropane hydrochloride (DOI) (1 mg/kg). Depletion of central 5-HT following systemic administration of the tryptophan hydroxylase inhibitor para-chlorophenylalanine (pCPA) produced effects similar to those observed with MDMA. Pre-treatment with the 5-HT receptor antagonist metergoline (4 mg/kg) or with the 5-HT reuptake inhibitor citalopram (30 mg/kg), however, failed to produce any effect alone or influence the response to MDMA. Pre-treatment with the dopamine D1 receptor antagonist SCH 23390 (1 mg/kg) failed to influence the changes in cortical perfusion obtained with MDMA. Treatment with the neuronal nitric oxide (NO) synthase inhibitor 7-nitroindazole (7-NI) (25 mg/kg) provoked no change in cerebral perfusion alone yet attenuated the MDMA-related increase in cortical perfusion.

CONCLUSIONS: Cortical 5-HT depletion is associated with increases in perfusion although this mechanism alone does not account for MDMA-related changes. A role for NO, a key regulator of cerebrovascular perfusion, is implicated in MDMA-induced increases in cortical perfusion.

Item Type
Publication Type
Irish-related, Article
Drug Type
CNS stimulants
1 November 2014
Identification #
doi: 10.1007/s00213-014-3790-0
Page Range
pp. 1501-1513
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