Tags

Type your tag names separated by a space and hit enter

Effect of acute brain tyrosine depletion on MDMA-induced changes in brain 5-HT.
J Psychopharmacol. 2010 Feb; 24(2):267-74.JP

Abstract

The mechanism by which 3,4-methylenedioxymethamphetamine (MDMA) produces 5-hydroxytryptamine (5-HT, serotonin) neurotoxicity has been suggested to involve an acute release of tyrosine and its non-enzymatic conversion to dopamine. To determine whether brain tyrosine availability is important in MDMA-induced neurotoxicity, brain tyrosine was acutely depleted with a tyrosine-free amino acid mixture (1 g/kg intraperitoneal; twice 1 h apart) which was administered prior to an injection of MDMA (12.5 mg/kg intraperitoneal). A small increase in both the hippocampal and striatal tyrosine concentration occurred in control rats treated with MDMA. The tyrosine-free amino acid mixture significantly decreased tyrosine levels by more than 50% in both brain regions 2 h after injection of either MDMA or saline. MDMA significantly reduced brain 5-HT content 2 h later, but this was of a similar magnitude in control and tyrosine-depleted groups. The long-term neurotoxic 5-HT loss in the hippocampus induced two weeks after MDMA administration was unaltered by the tyrosine-free amino acid mixture. Striatal dopamine content was unaffected by acute MDMA in all groups, while the tyrosine-free amino acid mixture given with MDMA significantly decreased striatal dopamine content 2 weeks later. The tyrosine-free amino acid mixture given alone had no affect on rectal body temperature but attenuated the duration of MDMA-induced hyperthermia. The results confirmed the ability of systemic MDMA to acutely increase brain tyrosine content, but also indicated that a marked acute reduction of brain tyrosine does not directly affect either immediate 5-HT release (as measured by tissue depletion) or long-term hippocampal serotonergic neurotoxicity produced by MDMA.

Authors+Show Affiliations

School of Biomedical Sciences, Institute of Neuroscience, University of Nottingham, Nottingham, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19965941

Citation

Rodsiri, R, et al. "Effect of Acute Brain Tyrosine Depletion On MDMA-induced Changes in Brain 5-HT." Journal of Psychopharmacology (Oxford, England), vol. 24, no. 2, 2010, pp. 267-74.
Rodsiri R, Green AR, Marsden CA, et al. Effect of acute brain tyrosine depletion on MDMA-induced changes in brain 5-HT. J Psychopharmacol (Oxford). 2010;24(2):267-74.
Rodsiri, R., Green, A. R., Marsden, C. A., & Fone, K. C. (2010). Effect of acute brain tyrosine depletion on MDMA-induced changes in brain 5-HT. Journal of Psychopharmacology (Oxford, England), 24(2), 267-74. https://doi.org/10.1177/0269881109348163
Rodsiri R, et al. Effect of Acute Brain Tyrosine Depletion On MDMA-induced Changes in Brain 5-HT. J Psychopharmacol (Oxford). 2010;24(2):267-74. PubMed PMID: 19965941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of acute brain tyrosine depletion on MDMA-induced changes in brain 5-HT. AU - Rodsiri,R, AU - Green,A R, AU - Marsden,C A, AU - Fone,K C F, Y1 - 2009/12/04/ PY - 2009/12/8/entrez PY - 2009/12/8/pubmed PY - 2010/4/27/medline SP - 267 EP - 74 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 24 IS - 2 N2 - The mechanism by which 3,4-methylenedioxymethamphetamine (MDMA) produces 5-hydroxytryptamine (5-HT, serotonin) neurotoxicity has been suggested to involve an acute release of tyrosine and its non-enzymatic conversion to dopamine. To determine whether brain tyrosine availability is important in MDMA-induced neurotoxicity, brain tyrosine was acutely depleted with a tyrosine-free amino acid mixture (1 g/kg intraperitoneal; twice 1 h apart) which was administered prior to an injection of MDMA (12.5 mg/kg intraperitoneal). A small increase in both the hippocampal and striatal tyrosine concentration occurred in control rats treated with MDMA. The tyrosine-free amino acid mixture significantly decreased tyrosine levels by more than 50% in both brain regions 2 h after injection of either MDMA or saline. MDMA significantly reduced brain 5-HT content 2 h later, but this was of a similar magnitude in control and tyrosine-depleted groups. The long-term neurotoxic 5-HT loss in the hippocampus induced two weeks after MDMA administration was unaltered by the tyrosine-free amino acid mixture. Striatal dopamine content was unaffected by acute MDMA in all groups, while the tyrosine-free amino acid mixture given with MDMA significantly decreased striatal dopamine content 2 weeks later. The tyrosine-free amino acid mixture given alone had no affect on rectal body temperature but attenuated the duration of MDMA-induced hyperthermia. The results confirmed the ability of systemic MDMA to acutely increase brain tyrosine content, but also indicated that a marked acute reduction of brain tyrosine does not directly affect either immediate 5-HT release (as measured by tissue depletion) or long-term hippocampal serotonergic neurotoxicity produced by MDMA. SN - 1461-7285 UR - https://www.unboundmedicine.com/medline/citation/19965941/Effect_of_acute_brain_tyrosine_depletion_on_MDMA_induced_changes_in_brain_5_HT_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881109348163?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -