Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.16.2 (
PCP
)
3,761
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could mitigate short-term episodic memory loss in a phencyclidine (
PCP
) model of schizophrenia. We then assessed whether changes in cortical or hippocampal GABA may underlie these effects. Female rats were ovariectomized and injected subchronically with
PCP
. To modulate E and LH, animals received estradiol capsules or Antide injections. Short-term episodic memory was assessed using the novel object recognition task (NORT). Brain expression of GAD67 was analyzed via western blot, and parvalbumin-containing cells were counted using immunohistochemistry. Some rats received hippocampal infusions of a GABA
A
agonist, GABA
A
antagonist, or GAD inhibitor before behavioral testing. We found that
PCP
reduced hippocampal GAD67 and abolished recognition memory. Antide restored hippocampal GAD67 and rescued recognition memory in
PCP
-treated animals.
Estradiol
prevented
PCP
's amnesic effect in NORT but failed to restore hippocampal GAD67.
PCP
did not cause significant differences in number of parvalbumin-expressing cells or cortical expression of GAD67. Hippocampal infusions of a GABA
A
agonist restored recognition memory in
PCP
-treated rats. Blocking hippocampal GAD or GABA
A
receptors in ovx animals reproduced recognition memory loss similar to
PCP
and inhibited estradiol's protection of recognition memory in
PCP
-treated animals. In summary, decreasing LH or increasing E can lessen short-term episodic memory loss, as measured by novel object recognition, in a
PCP
model of schizophrenia. Alterations in hippocampal GABA may contribute to both
PCP
's effects on recognition memory and the hormones' ability to prevent or reverse them.
...
PMID:Estradiol and luteinizing hormone regulate recognition memory following subchronic phencyclidine: Evidence for hippocampal GABA action. 2952 24
