PMID- 25366875
OWN - NLM
STAT- MEDLINE
DCOM- 20151120
LR  - 20181113
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 232
IP  - 9
DP  - 2015 May
TI  - Investigation of the mechanisms mediating MDMA "Ecstasy"-induced increases in 
      cerebro-cortical perfusion determined by btASL MRI.
PG  - 1501-13
LID - 10.1007/s00213-014-3790-0 [doi]
AB  - 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.
FAU - Rouine, J
AU  - Rouine J
AD  - Trinity College Institute of Neuroscience, Trinity College, Dublin, 2, Ireland.
FAU - Kelly, M E
AU  - Kelly ME
FAU - Jennings-Murphy, C
AU  - Jennings-Murphy C
FAU - Duffy, P
AU  - Duffy P
FAU - Gorman, I
AU  - Gorman I
FAU - Gormley, S
AU  - Gormley S
FAU - Kerskens, C M
AU  - Kerskens CM
FAU - Harkin, Andrew
AU  - Harkin A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141101
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 0 (Spin Labels)
RN  - 0DHU5B8D6V (Citalopram)
RN  - 2DS058H2CF (Fenfluramine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - R5J7E3L9SP (Fenclonine)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects
MH  - Cerebrovascular Circulation/*drug effects
MH  - Citalopram/pharmacology
MH  - Dopamine Antagonists/pharmacology
MH  - Fenclonine/pharmacology
MH  - Fenfluramine/pharmacology
MH  - Magnetic Resonance Imaging/methods
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin Antagonists/pharmacology
MH  - Serotonin Receptor Agonists/pharmacology
MH  - Spin Labels
EDAT- 2014/11/05 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/11/05 06:00
PHST- 2014/10/16 00:00 [received]
PHST- 2014/10/19 00:00 [accepted]
PHST- 2014/11/05 06:00 [entrez]
PHST- 2014/11/05 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 10.1007/s00213-014-3790-0 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2015 May;232(9):1501-13. doi: 
      10.1007/s00213-014-3790-0. Epub 2014 Nov 1.