Acute amygdalar activation induces an upregulation of multiple monoamine G protein coupled pathways in rat hippocampus.
A "partial" rodent model for schizophrenia has been used to characterize the regulation of hippocampal genes in response to amygdalar activation. At 96 h after the administration of picrotoxin into the basolateral nucleus, we have observed an increase in the expression of genes associated with 18 different monoamine (ie adrenergic alpha 1, alpha 2 and beta 2, serotonergic 5HT5b and 5HT6, dopamine D4 and muscarinic m1, m2 and m3) and peptide (CCK A and B, angiotensin 1A, mu and kappa opiate, FSH, TSH, LH, GNRH, and neuropeptide Y) G-protein coupled receptors (GPCRs). These latter receptors are associated with three different G protein signaling pathways (Gq, Gs, and Gi) in which significant changes in gene expression were also noted for adenylate cyclase (AC4), phosphodiesterase (PDE4D), protein kinase A (PKA), and protein kinase C (PKC). Quantitative RT-PCR was used to validate the results and demonstrated that there were predictable increases of three GPCRs selected for this analysis, including the dopamine D4, alpha 1b, and CCK-B receptors. Eight out of the nine monoamine receptors showing these changes have moderate to high affinity for the atypical antipsychotic, clozapine. Taken together, these results suggest that amygdalar activation may play a role in the pathophysiology and treatment of psychosis by regulating the activity of multiple GPCR and metabolic pathways in hippocampal cells.
Benes
F M
FM
Program in Structural and Molecular Neuroscience, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. benesf@mclean.harvard.edu
Burke
R E
RE
Walsh
J
J
Berretta
S
S
Matzilevich
D
D
Minns
M
M
Konradi
C
C
D000679:Amygdala / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D004195:Disease Models, Animal; D031541:Fluorescence Resonance Energy Transfer; D019204:GTP-Binding Proteins / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D007267:Injections; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010852:Picrotoxin / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000503:physiopathology*
D015306:Biogenic Monoamines; D019204:GTP-Binding Proteins; D010852:Picrotoxin; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter