5-HT1A agonist and dexamethasone reversal of para-chloroamphetamine induced loss of MAP-2 and synaptophysin immunoreactivity in adult rat brain.
Serotonin and dexamethasone act as differentiating agents during development. Reducing circulating adrenal steroids or central 5-HT levels via adrenalectomy (ADX) or the tryptophan hydroxylase inhibitor, para-chlorophenylalanine (PCPA), respectively, has been shown to have de-differentiating effects in the adult brain. Morphometric analysis of 5-HT, S100 beta, MAP-2 and synaptophysin immunoreactivity (IR) was used to follow the molecular plasticity of several brain regions after lesioning of 5-HT nerve terminals by para-chloroamphetamine (PCA; 2 x 10 mg/kg s.c.), a serotonin neurotoxin. Two weeks after PCA treatment we observed reductions of 5-HT, S100 beta, and MAP-2 IR in parietal and temporal cortex, temporal pole, hippocampus and hypothalamus. The reductions in MAP-2 and synaptophysin-IR were reversed by 3 days of treatment with dexamethasone (10 mg/l drinking water) or ipsapirone, a 5-HT1A agonist (1 mg/kg s.c.). The loss of S100-IR was reversed only by the 5-HT1A agonist. These results indicate that both dexamethasone and serotonin have effects on adult neuronal plasticity but may work via different mechanisms. The implications of these findings to the loss of synaptophysin and MAP-2 staining in Alzheimer's disease are discussed.
Azmitia
E C
EC
Department of Biology, New York University, NY 10003, USA.
Rubinstein
V J
VJ
Strafaci
J A
JA
Rios
J C
JC
Whitaker-Azmitia
P M
PM
D000367:Age Factors; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001923:Brain Chemistry / Q000276:immunology; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology; D003907:Dexamethasone / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000187:drug effects* / Q000276:immunology*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000187:drug effects / Q000276:immunology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D016708:Synaptophysin / Q000187:drug effects* / Q000276:immunology*; D010133:p-Chloroamphetamine / Q000494:pharmacology
D008869:Microtubule-Associated Proteins; D009418:S100 Proteins; D017366:Serotonin Receptor Agonists; D016708:Synaptophysin; D010133:p-Chloroamphetamine; D003907:Dexamethasone