PMID- 14644466
OWN - NLM
STAT- MEDLINE
DCOM- 20040311
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 995
IP  - 1
DP  - 2004 Jan 2
TI  - Short-term, D2 receptor blockade induces synaptic degeneration, reduces levels of 
      tyrosine hydroxylase and brain-derived neurotrophic factor, and enhances 
      D2-mediated firing in the ventral pallidum.
PG  - 14-22
AB  - Repeated treatments with neuroleptics are associated with biochemical and 
      morphological alterations in forebrain neurons as well as an upregulation of 
      D2-mediated changes in neuronal function. The present study evaluated the 
      histological and physiological effects of three once-daily treatments with two 
      chemically divergent neuroleptics, haloperidol (1 mg/kg i.p./day) and eticlopride 
      (3 mg/kg i.p./day), measured in rats 24 h after the last injection. It was 
      determined that this short-term antagonism of D2-like receptors induced fiber and 
      terminal degeneration and significantly decreased tyrosine hydroxylase (TH) and 
      brain-derived neurotrophic factor (BDNF) immunoreactivity in the ventral pallidum 
      (VP), as determined by optical density measurements. While other forebrain 
      regions demonstrated changes in TH and BDNF, the neurodegeneration profile was 
      unique to the VP. This was accompanied by an enhancement in the efficacy of the 
      D2 agonist quinpirole to increase spiking rate of VP neurons recorded in chloral 
      hydrate-anesthetized rats. These data indicate that short-term treatments with D2 
      antagonists are sufficient to induce changes in the biochemical and morphological 
      profiles uniquely within the VP. Moreover, the functional ramifications of these 
      changes appear to include profound alterations in the way dopamine regulates 
      neuronal activity in this region.
FAU - Meredith, G E
AU  - Meredith GE
AD  - Department of Cellular and Molecular Pharmacology, The Chicago Medical School, 
      Finch University of Health Sciences, 3333 Green Bay Rd., North Chicago, IL 
      60064-3095, USA. Gloria.Meredith@finchcms.edu
FAU - Switzer, R C 3rd
AU  - Switzer RC 3rd
FAU - Napier, T C
AU  - Napier TC
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Agonists)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Dopamine D2 Receptor Antagonists)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Salicylamides)
RN  - 20OP60125T (Quinpirole)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - J6292F8L3D (Haloperidol)
RN  - J8M468HBH4 (eticlopride)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Antipsychotic Agents/*toxicity
MH  - Brain-Derived Neurotrophic Factor/drug effects/*metabolism
MH  - Cell Survival/drug effects/physiology
MH  - Disease Models, Animal
MH  - Dopamine/biosynthesis
MH  - Dopamine Agonists/pharmacology
MH  - Dopamine Antagonists/toxicity
MH  - *Dopamine D2 Receptor Antagonists
MH  - Drug Administration Schedule
MH  - Dyskinesia, Drug-Induced/metabolism/pathology
MH  - Haloperidol/toxicity
MH  - Immunohistochemistry
MH  - Male
MH  - Microscopy, Electron
MH  - Nerve Degeneration/chemically induced/metabolism/pathology
MH  - Presynaptic Terminals/*drug effects/pathology/ultrastructure
MH  - Prosencephalon/*drug effects/metabolism/ultrastructure
MH  - Quinpirole/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Dopamine D2/metabolism
MH  - Salicylamides/toxicity
MH  - Synaptic Transmission/drug effects/physiology
MH  - Tyrosine 3-Monooxygenase/*metabolism
EDAT- 2003/12/04 05:00
MHDA- 2004/03/12 05:00
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/03/12 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
AID - S0006899303037582 [pii]
AID - 10.1016/j.brainres.2003.09.040 [doi]
PST - ppublish
SO  - Brain Res. 2004 Jan 2;995(1):14-22. doi: 10.1016/j.brainres.2003.09.040.