PMID- 30665313
OWN - NLM
STAT- MEDLINE
DCOM- 20200527
LR  - 20200527
IS  - 1461-7285 (Electronic)
IS  - 0269-8811 (Linking)
VI  - 33
IP  - 3
DP  - 2019 Mar
TI  - A genetic deletion of the serotonin transporter differentially influences the 
      behavioural effects of MDMA.
PG  - 355-363
LID - 10.1177/0269881118822156 [doi]
AB  - BACKGROUND: While (+/-)-3,4-methylenedioxymethamphetamine (MDMA) primarily induces 
      serotonin release, it also affects dopamine and noradrenaline transmission. It 
      is, however, unclear what role each of these neurotransmitters play in the 
      behavioural profile of MDMA. METHODS: In this study we used the drug 
      discrimination (DD) and the acoustic startle (ASR) paradigms to examine the 
      behaviour of rats with and without a genetic deletion of the serotonin 
      transporter SERT (SERT(-/-) and SERT(+/+) rats). In DD, rats were trained to 
      respond on different levers following an injection of 1.5 mg/kg MDMA, or saline. 
      After acquisition, they were given a challenge dose of 0.5 mg/kg amphetamine 
      (AMPH). In the ASR paradigm, SERT(+/+) and SERT(-/-) rats were given 0, 5 or 10 
      mg/kg MDMA. RESULTS: In DD, significantly fewer SERT(-/-) rats acquired MDMA 
      discrimination. When the acquirers were challenged with AMPH, SERT(+/+) showed 
      partial, while SERT(-/-) rats showed full generalisation to MDMA. In the ASR 
      paradigm, MDMA significantly reduced prepulse inhibition and startle habituation 
      in SERT(+/+) rats, while having no effect in SERT(-/-) rats. CONCLUSION: Together 
      these data suggest that in wildtype rats the interoceptive cues of MDMA are 
      primarily mediated by serotonin and to a lesser extent by dopamine and 
      noradrenaline, while the effects in the startle paradigm are almost exclusively 
      mediated via serotonin. Together, these data contribute to our understanding of 
      the complex pharmacodynamics of MDMA.
FAU - Pettie, Michaela
AU  - Pettie M
AD  - School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
FAU - Oakly, Alana
AU  - Oakly A
AD  - School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
FAU - Harper, David N
AU  - Harper DN
AD  - School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
FAU - Ellenbroek, Bart A
AU  - Ellenbroek BA
AUID- ORCID: 0000-0003-1996-4873
AD  - School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190122
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (Hallucinogens)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Discrimination, Psychological/drug effects
MH  - Dopamine/metabolism
MH  - Gene Deletion
MH  - Gene Knockout Techniques
MH  - Hallucinogens/*pharmacology
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Norepinephrine/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reflex, Startle/drug effects
MH  - Serotonin/metabolism
MH  - Serotonin Agents/pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins/*genetics
OTO - NOTNLM
OT  - Drug discrimination
OT  - amphetamine
OT  - prepulse inhibition
OT  - serotonin transporter knock-out rats
EDAT- 2019/01/23 06:00
MHDA- 2020/05/28 06:00
CRDT- 2019/01/23 06:00
PHST- 2019/01/23 06:00 [pubmed]
PHST- 2020/05/28 06:00 [medline]
PHST- 2019/01/23 06:00 [entrez]
AID - 10.1177/0269881118822156 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2019 Mar;33(3):355-363. doi: 10.1177/0269881118822156. Epub 
      2019 Jan 22.