PMID- 24618531
OWN - NLM
STAT- MEDLINE
DCOM- 20150529
LR  - 20240314
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 3
DP  - 2014
TI  - Testosterone induces molecular changes in dopamine signaling pathway molecules in 
      the adolescent male rat nigrostriatal pathway.
PG  - e91151
LID - 10.1371/journal.pone.0091151 [doi]
LID - e91151
AB  - Adolescent males have an increased risk of developing schizophrenia, implicating 
      testosterone in the precipitation of dopamine-related psychopathology. Evidence 
      from adult rodent brain indicates that testosterone can modulate nigrostriatal 
      dopamine. However, studies are required to understand the role testosterone plays 
      in maturation of dopamine pathways during adolescence and to elucidate the 
      molecular mechanism(s) by which testosterone exerts its effects. We hypothesized 
      that molecular indices of dopamine neurotransmission [synthesis (tyrosine 
      hydroxylase), breakdown (catechol-O-methyl transferase; monoamine oxygenase), 
      transport [vesicular monoamine transporter (VMAT), dopamine transporter (DAT)] 
      and receptors (DRD1-D5)] would be changed by testosterone or its metabolites, 
      dihydrotestosterone and 17beta-estradiol, in the nigrostriatal pathway of adolescent 
      male rats. We found that testosterone and dihydrotestosterone increased DAT and 
      VMAT mRNAs in the substantia nigra and that testosterone increased DAT protein at 
      the region of the cell bodies, but not in target regions in the striatum. 
      Dopamine receptor D2 mRNA was increased and D3 mRNA was decreased in substantia 
      nigra and/or striatum by androgens. These data suggest that increased 
      testosterone at adolescence may change dopamine responsivity of the nigrostriatal 
      pathway by modulating, at a molecular level, the capacity of neurons to transport 
      and respond to dopamine. Further, dopamine turnover was increased in the dorsal 
      striatum following gonadectomy and this was prevented by testosterone 
      replacement. Gene expression changes in the dopaminergic cell body region may 
      serve to modulate both dendritic dopamine feedback inhibition and reuptake in the 
      dopaminergic somatodendritic field as well as dopamine release and re-uptake 
      dynamics at the presynaptic terminals in the striatum. These testosterone-induced 
      changes of molecular indices of dopamine neurotransmission in males are primarily 
      androgen receptor-driven events as estradiol had minimal effect. We conclude that 
      nigrostriatal responsivity to dopamine may be modulated by testosterone acting 
      via androgen receptors to alter gene expression of molecules involved in dopamine 
      signaling during adolescence.
FAU - Purves-Tyson, Tertia D
AU  - Purves-Tyson TD
AD  - Schizophrenia Research Institute, Sydney, New South Wales, Australia; 
      Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, New 
      South Wales, Australia; School of Medical Sciences, University of New South 
      Wales, Sydney, New South Wales, Australia.
FAU - Owens, Samantha J
AU  - Owens SJ
AD  - Schizophrenia Research Institute, Sydney, New South Wales, Australia; 
      Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, New 
      South Wales, Australia; School of Medical Sciences, University of New South 
      Wales, Sydney, New South Wales, Australia.
FAU - Double, Kay L
AU  - Double KL
AD  - Discipline of Biomedical Science, School of Medical Sciences, Sydney Medical 
      School, University of Sydney, Sydney, New South Wales, Australia.
FAU - Desai, Reena
AU  - Desai R
AD  - ANZAC Research Institute, University of Sydney, Concord Hospital, Concord, New 
      South Wales, Australia.
FAU - Handelsman, David J
AU  - Handelsman DJ
AD  - ANZAC Research Institute, University of Sydney, Concord Hospital, Concord, New 
      South Wales, Australia.
FAU - Weickert, Cynthia Shannon
AU  - Weickert CS
AD  - Schizophrenia Research Institute, Sydney, New South Wales, Australia; 
      Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, New 
      South Wales, Australia; School of Psychiatry, University of New South Wales, 
      Sydney, New South Wales, Australia.
LA  - eng
PT  - Journal Article
DEP - 20140311
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Gonadal Steroid Hormones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Dopamine)
RN  - 3XMK78S47O (Testosterone)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Corpus Striatum/*drug effects/*metabolism
MH  - Dopamine/*metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/genetics/metabolism
MH  - Gene Expression Regulation
MH  - Gonadal Steroid Hormones/blood
MH  - Male
MH  - Orchiectomy
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Receptors, Dopamine/genetics/metabolism
MH  - Signal Transduction/*drug effects
MH  - Substantia Nigra/*drug effects/*metabolism
MH  - Synaptic Transmission/drug effects
MH  - Testosterone/*pharmacology
PMC - PMC3949980
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/03/13 06:00
MHDA- 2015/05/30 06:00
PMCR- 2014/03/11
CRDT- 2014/03/13 06:00
PHST- 2012/12/05 00:00 [received]
PHST- 2014/02/10 00:00 [accepted]
PHST- 2014/03/13 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2015/05/30 06:00 [medline]
PHST- 2014/03/11 00:00 [pmc-release]
AID - PONE-D-12-38348 [pii]
AID - 10.1371/journal.pone.0091151 [doi]
PST - epublish
SO  - PLoS One. 2014 Mar 11;9(3):e91151. doi: 10.1371/journal.pone.0091151. eCollection 
      2014.